Rx for CHANGE Clinician-Assisted Tobacco Cessation

Rx for CHANGE Clinician-Assisted Tobacco Cessation
♪ Note to instructor(s): Please update this slide by inserting instructor name(s).

TRAINING OVERVIEW Epidemiology of Tobacco Use module
Forms of Tobacco module Nicotine Pharmacology & Principles of Addiction module Drug Interactions with Smoking module Assisting Patients with Quitting module Hands-on workshop Aids for Cessation module Tobacco trigger tapes Case scenarios ♪ Note to instructor(s): This program is divided into two major sections: Didactic lecture (core and optional modules) Hands-on workshop (Aids for Cessation module, trigger tapes, and case scenarios for role playing) The following modules are considered core components (i.e., essential to the training): Epidemiology of Tobacco Use Forms of Tobacco Nicotine Pharmacology & Principles of Addiction Drug Interactions with Smoking Assisting Patients with Quitting – available in two versions: 1. The Clinical Practice Guideline version, which categorizes smokers as not ready to quit, ready to quit (in the next 30 days), a recent quitter, or a former smoker 2. The Transtheoretical Model of Change version, which categorizes smokers as being in the precontemplation, contemplation, preparation, action, or maintenance stage of change for quitting In addition, a hands-on workshop can include the following components: Aids for Cessation module Tobacco trigger tapes Role playing with case scenarios The Forms of Tobacco module is an optional but highly recommended module. Other optional modules include Pathophysiology of Tobacco-Related Disease, Post-Cessation Weight Maintenance, Genes and Tobacco Use, A History of Tobacco Control Efforts, How to Get Involved, and Tobacco Use: Adolescents and Young Adults. Please update this slide to reflect the modules that you will be teaching.

EPIDEMIOLOGY of TOBACCO USE
This module focuses on the epidemiology of tobacco use and provides an overview of adverse health consequences associated with tobacco use. For more detailed explanations of the adverse health consequences of tobacco use, refer to the Pathophysiology of Tobacco-Related Disease module (optional).

is the chief, single, avoidable cause of death
“CIGARETTE SMOKING… is the chief, single, avoidable cause of death in our society and the most important public health issue of our time.” As the former U.S. Surgeon General C. Everett Koop noted, “Cigarette smoking is the chief, single, avoidable cause of death in our society and the most important public health issue of our time” (USDHHS, 1982). This statement was published in a Surgeon General’s report in 1982 and remains true today, more than two decades later. It is well established that smoking harms nearly every organ in the body, causing a wide range of diseases and reducing quality of life and life expectancy (USDHHS, 2004). Approximately 100 million persons died due to tobacco use in the 20th century—which is just a fraction of the number that we anticipate losing during the 21st century. In 2000, an estimated 4.83 million premature deaths occurred worldwide due to tobacco—2.41 million in developing countries and 2.43 million in industrialized nations (Ezzati & Lopez, 2003). Epidemiologist Richard Peto (2000) predicted that an additional 900 million persons are likely to die due to tobacco use over the next 100 years, if the current trends continue, bringing the two-century death toll to 1 billion lives lost. As the death toll continues to rise, public health advocates continue to work toward identifying effective ways to (1) prevent the onset of tobacco use and (2) help patients quit using tobacco. Health care professionals can have an important public health impact by helping to counter tobacco use. However, research studies consistently demonstrate that students in the health professions receive insufficient training for providing comprehensive tobacco cessation counseling. Ezzati M, Lopez AD. (2003). Estimates of global mortality attributable to smoking in Lancet 362:847–852. Peto R. (2000, November). Presented at Society for Research on Nicotine and Tobacco international meeting, London, England. U.S. Department of Health and Human Services (USDHHS). (1982). The Health Consequences of Smoking: Cancer. A Report of the Surgeon General (DHHS Publication No. PHS ). Rockville, MD: Public Health Service, Office on Smoking and Health. U.S. Department of Health and Human Services. (2004). The Health Consequences of Smoking: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. C. Everett Koop, M.D., former U.S. Surgeon General

WORLDWIDE ADULT TOBACCO USE PREVALENCE (Men/Women)
France 34.5 (38.6/30.3) Sweden 19.0 (19.0/19.0) Yugoslavia 47.0 (52.0/42.0) Canada 25.0 (27.0/23.0) Russian Federation 36.5 (63.2/9.7) UK 26.5 (27.0/26.0) China 35.6 (66.9/4.2) USA 20.9 (23.9/18.1) The prevalence of tobacco use varies among countries, and in many countries it varies greatly between men and women (CDC, 2006; Mackay & Erickson, 2002). In developed countries, approximately 22% of women and 35% of men smoke tobacco, compared with developing countries, in which 9% of women and 50% of men smoke. The trends in male smoking prevalence have peaked or are declining slowly in developed and developing countries. The smoking prevalence among women is declining in many developed countries (U.S., Canada, U.K., and Australia); however, in other developed countries (e.g., central, southern, and eastern Europe), the prevalence is either remaining constant or increasing. In Norway, Sweden, and New Zealand the smoking prevalence is similar among men and women. The male smoking prevalence in China, Asia, Russia, and eastern European countries is high (>40%). In China, more than 300 million men smoke; this number is comparable to the entire population of the U.S. One in three cigarettes consumed in the world today is smoked in China (Mackay & Erickson, 2002). Centers for Disease Control and Prevention. (2006). Tobacco use among adults—United States, MMWR 55:1145–1148. Mackay J, Erickson M. (2002). The Tobacco Atlas. Geneva, Switzerland: World Health Organization. Retrieved December 31, 2006, from Japan 33.1 (52.8/13.4) Philippines 32.4 (53.8/11.0) Guinea 51.7 (59.5/43.8) Iran 15.3 (27.2/3.4) India 16.0 (29.4/2.5) Brazil 33.8 (38.2/29.3) Australia 19.5 (21.1/18.0) Namibia 50.0 (65.0/35.0) South Africa 26.5 (42.0/11.0) New Zealand 25.0 (25.0/25.0) Mackay & Erickson. (2002). The Tobacco Atlas. World Health Organization.

TRENDS in ADULT CIGARETTE CONSUMPTION—U.S., 1900–2005
Annual adult per capita cigarette consumption and major smoking and health events Master Settlement Agreement; California first state to enact ban on smoking in bars 1964 Surgeon General’s Report Broadcast ad ban End of WW II Early in the 20th century, several events coincided that contributed to increases in annual per-capita cigarette consumption, including the introduction of blends and curing processes that allowed the inhalation of tobacco, the invention of the safety match, improvements in mass production, transportation that permitted widespread distribution of cigarettes, and the use of mass media advertising to promote cigarettes (USDHHS, 1995). Cigarette smoking among women began to increase in the 1920s, when targeted industry marketing and social changes reflecting the liberalization of women's roles and behavior led to the increasing acceptability of smoking among women (USDHHS,1980; Waldron, 1991). Annual per-capita cigarette consumption by adults (i.e., 18 years or older) increased dramatically from 54 cigarettes in 1900 to a peak of 4,345 cigarettes in 1963 (CDC, 1994). For the year 2005, per-capita consumption was estimated at 1,716 cigarettes per person, a 3% drop from 1,791 in 2004 (USDA, 2006). Some decreases correlate with events such as the first research suggesting a link between smoking and cancer in the 1950s, the 1964 Surgeon General’s Report, and increased tobacco taxation and industry price increases during the 1980s. In 1998, the year of the Master Settlement Agreement, California was the first state to enact a ban on smoking in bars. By the end of 2006, more than 20 states had a tax of at least $1.00 per pack on cigarettes. Centers for Disease Control and Prevention (CDC). (1994). Surveillance for selected tobacco-use behaviors—United States, 1900–1994. MMWR 43 (no. SS-3). U.S. Department of Agriculture (USDA), Economic Research Service. (2006, April 28). Tobacco Outlook. Report TBS-260. Retrieved December 31, 2006, from U.S. Department of Health and Human Services (USDHHS). (1995). For a Healthy Nation: Returns on Investment in Public Health. Atlanta, GA: Public Health Service, Office of Disease Prevention and Health Promotion and CDC. U.S. Department of Health and Human Services. (1980). The Health Consequences of Smoking for Women. A Report of the Surgeon General. Washington, DC: Public Health Service, Office on Smoking and Health. Waldron I. (1991). Patterns and causes of gender differences in smoking. Soc Sci Med 32:989–1005. Number of cigarettes Marketing of filtered cigarettes U.S. entry into WW I Nonsmokers’ rights movement begins Cigarette price drop First modern reports linking smoking and cancer 20 states have > $1 pack tax Federal cigarette tax doubles Great Depression Year Centers for Disease Control and Prevention. (1999). MMWR 48:986–993. Per-capita updates from U.S. Department of Agriculture, provided by the American Cancer Society.

ADULT PER-CAPITA CONSUMPTION of TOBACCO, 1880–2005
All forms of tobacco are harmful. This figure depicts the shifts in per-capita consumption for the various tobacco products in the U.S. between 1880 and 2005 (Thun et al., 2002; updates from the U.S. Department of Agriculture). During the late 19th and early 20th centuries, tobacco use was predominantly in the form of chewing tobacco, cigars, pipes, and snuff. Now, the cigarette is the leading form of tobacco use in the United States. All forms of tobacco are harmful. Thun MJ, Henley SJ, Calle EE. (2002). Tobacco use and cancer: An epidemiologic perspective for geneticists. Oncogene 21:7307–7325. Year Adapted from NCI Smoking and Tobacco Control Monograph 8, 1997, p. 13. Data from U.S. Department of Agriculture. Reprinted with permission. Thun et al Oncogene 21:7307–7325.

TRENDS in ADULT SMOKING, by SEX—U.S., 1955–2005
Trends in cigarette current smoking among persons aged 18 or older 20.9% of adults are current smokers Male Percent This graph demonstrates trends in smoking among adults in the U.S. between 1955 and 2005 (CDC, 1999, 2006). Since 1990, the smoking prevalence among men and women has experienced only a slight decline, compared to previous decades, highlighting a need for enhanced tobacco control efforts. In 2005, results of the National Health Interview Survey (NHIS) indicated that approximately 45.1 million adults (20.9% of the U.S. adult population) are current smokers1 (CDC, 2006). Of these, 80.8% smoke every day and 19.2% smoke some days (CDC, 2006). More men (23.9%) than women (18.1%) are current smokers. An estimated 70% of all smokers want to quit completely (CDC, 2002). In 2005, approximately 19.2 million (42.5%) of current smokers stopped smoking at least 1 day during the past 12 months because they were trying to quit (CDC, 2006). In 2005, an estimated 46.5 million adults were former smokers,2 representing 50.8% of persons who had ever smoked (CDC, 2006). ♪ Note to instructor(s): Cessation statistics vary depending on factors such as the duration of follow-up, definitions of abstinence, and whether reports of cessation were biologically confirmed. According to the CDC (2002), 4.7% of smokers who had smoked every day or some days during the past year had quit and were able to maintain abstinence for 3–12 months in 2000. 1Current smokers: persons who reported having smoked 100 or more cigarettes during their lifetime and who smoked every day or some days at the time of the interview. 2Former smokers: persons who reported having smoked 100 or more cigarettes during their lifetime but currently did not smoke. Centers for Disease Control and Prevention (CDC). (1999). Achievements in public health, 1900–1999: Tobacco use—United States, 1900–1999. MMWR 48:986–993. Centers for Disease Control and Prevention. (2002). Cigarette smoking among adults—United States, MMWR 51:642–645. Centers for Disease Control and Prevention. (2006). Tobacco use among adults—United States, MMWR 55:1145–1148. 23.9% Female 18.1% Year 70% want to quit Graph provided by the Centers for Disease Control and Prevention Current Population Survey; 1965–2005 NHIS. Estimates since 1992 include some-day smoking.

STATE-SPECIFIC PREVALENCE of SMOKING among ADULTS, 2005
Illinois 19.9% California 15.2% Kentucky 28.7% The prevalence of smoking among adults varies widely across the U.S., ranging from 11.5% in Utah to 28.7% in Kentucky (data from 2005 Behavioral Risk Factor Surveillance System; CDC, 2006). ♪ Note to instructor(s): State-specific prevalence estimates for California, Illinois, Kentucky, Nevada, New York, Texas, and Utah are provided for comparison purposes. Please edit this slide to include the prevalence for your state. The 2004 prevalence statistics for all states are provided at Most of the states with the highest smoking prevalence have the lowest state taxes on cigarettes. The state cigarette excise tax varies widely by state and ranges from a high of $2.58 per pack in New Jersey to 7 cents per pack in South Carolina. The major tobacco states (KY, VA, NC, SC, GA, TN) average 26.5 cents per pack; other states average $1.09 per pack. Overall, the average is $1.00 per pack. The federal cigarette tax is 39 cents per pack. State cigarette excise tax rates and rankings as of November 17, 2006, for several states (rank shown on left, out of 50 states and Washington, DC) (Campaign for Tobacco-Free Kids, 2006): 1 New Jersey – $2.58 2 Rhode Island – $2.46 3 Washington – $2.025 4,5,6 Arizona, Maine, Michigan – $2.00 44 North Carolina – $0.35 46,47 Kentucky, Virginia – $0.30 48 Tennessee – $0.20 49 Mississippi – $0.18 50 Missouri – $0.17 51 South Carolina – $0.07 ♪ Note to instructor(s): Excise taxes for each state are available on the Campaign for Tobacco-Free Kids fact sheet, which is updated regularly to reflect changes in legislation. Campaign for Tobacco-Free Kids. (2006). “State Cigarette Excise Tax Rates & Rankings.” Retrieved December 31, 2006, from Centers for Disease Control and Prevention (CDC). (2006). State-specific prevalence of cigarette smoking among adults and secondhand smoke rules and policies in homes and workplaces—United States, MMWR 55:1148–1151. Nevada 23.1% New York 20.5% Utah 11.5% Florida 21.6% Texas 20.0% Indiana 27.3% Centers for Disease Control and Prevention. (2006). MMWR 55:1148–1151.

PREVALENCE of ADULT SMOKING, by RACE/ETHNICITY—U.S., 2005
32.0% American Indian/Alaska Native* 21.9% White* In 2005, the prevalence of smoking in the U.S. was highest among American Indian/Alaska Natives (32.0%) and next highest among non-Hispanic Whites (21.9%), followed by non-Hispanic Blacks (21.5%), Hispanics (16.2%), and Asians (13.3%) (CDC, 2006). Centers for Disease Control and Prevention. (2006). Tobacco use among adults—United States, MMWR 55:1145–1148. 21.5% Black* 16.2% Hispanic 13.3% Asian* * non-Hispanic. Centers for Disease Control and Prevention. (2006). MMWR 55:1145–1148.

PREVALENCE of ADULT SMOKING, by EDUCATION—U.S., 2005
25.5% No high school diploma 43.2% GED diploma In 2005, the prevalence of current smoking1 in the U.S. was highest among adults (aged 25 years or older) who had received a General Educational Development (GED) diploma (43.2%). Persons with a graduate degree (masters, professional, or doctorate) had the lowest prevalence (7.1%) (CDC, 2006). Also notable is the fact that the prevalence of adult smoking is associated with poverty level. The prevalence is 20.6% for persons who are at or above the poverty level and 29.9% for persons who are below the poverty level (CDC, 2006). The smoking prevalence is 24.4% for persons aged 18–24; 24.1% for persons aged 25–44; 21.9% for persons aged 45–64; and 8.6% for persons at least 65 years of age (CDC, 2006). 1Current smokers: persons who reported having smoked 100 or more cigarettes during their lifetime and who smoked every day or some days at the time of the interview. Centers for Disease Control and Prevention. (2006). Tobacco use among adults—United States, MMWR 55:1145–1148. 24.6% High school graduate 22.5% Some college 10.7% Undergraduate degree 7.1% Graduate degree Centers for Disease Control and Prevention. (2006). MMWR 55:1145–1148.

TRENDS in TEEN SMOKING, by ETHNICITY—U.S., 1977–2006
Trends in cigarette smoking among 12th graders: 30-day prevalence of use White Cigarette smoking among adolescents is a public health concern of utmost importance. In the U.S., experimentation with cigarettes and the development of regular smoking typically occur during adolescence, with 89% of adult smokers having tried their first cigarette by 18 years of age (Gilpin et al., 1999; USDHHS, 1994), and 71% of adult daily smokers having become regular smokers by age 18 (Gilpin et al., 1999). Each day, an estimated 3,000 additional children and adolescents become established smokers (Gilpin et al., 1999). Because most youth who smoke at least monthly continue to smoke in adulthood, tobacco use trends among youth are a key indicator of the overall health trends for the U.S. (USDHHS, 2000). During 1991–1997, the smoking prevalence (defined as one or more cigarettes in the 30 days before survey completion) among high school seniors increased to 36.5%. At that time, the prevalence was highest among whites (40.7%) and lowest among blacks (14.3%). This worrisome increasing trend highlighted a need for tobacco prevention and cessation programs focused on this age group. In 2006, an estimated 21.6% of 12th graders (22.4% of males and 20.1% of females) had smoked one or more cigarettes in the past 30 days. Among 8th- and 10th-grade students in 2006, the overall 30-day point prevalence for cigarette smoking was 8.7% and 14.5%, respectively (Johnston et al., 2006). As can be seen in the graph, smoking among adolescents has declined over the past decade; however, the downward trend has largely diminished in recent years. ♪ Note to instructor(s): Monitoring the Future data, publications, and press releases are available at Gilpin EA, Choi WS, Berry C, Pierce JP. (1999). How many adolescents start smoking each day in the United States? J Adolesc Health 25:248–255. Johnston LD, O'Malley PM, Bachman JG, Schulenberg, JE. (2006). Decline in daily smoking by younger teens has ended. University of Michigan News and Information Services: Ann Arbor, MI. Data retrieved December 31, 2006 from U.S. Department of Health and Human Services (USDHHS). (1994). Preventing Tobacco Use Among Young People: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking Health. U.S. Department of Health and Human Services. (2000). Healthy People Washington, DC: U.S. Department of Health and Human Services. Percent Hispanic Black Institute for Social Research, University of Michigan, Monitoring the Future Project

PUBLIC HEALTH versus “BIG TOBACCO”
The biggest opponent to tobacco control efforts is the tobacco industry itself. Historically, public health efforts to reduce tobacco-related morbidity and mortality have faced strong opposition. The biggest opponent to tobacco control efforts is the tobacco industry itself. It has been estimated that for every $1 spent by the states on tobacco prevention initiatives, the tobacco industry spends approximately $28 to market its products (Campaign for Tobacco-Free Kids, 2005; FTC, 2005). Campaign for Tobacco-Free Kids. (2005). “State Tobacco-Prevention Spending vs. Tobacco Company Marketing.” Retrieved December 31, 2006, from Federal Trade Commission (FTC). (2005). Cigarette Report for Retrieved December 31, 2006, from In the U.S., for every $1 spent on tobacco prevention, the tobacco industry spends $28 to market its products.

The TOBACCO INDUSTRY For decades, the tobacco industry has publicly denied the addictive nature of nicotine and the negative health effects of tobacco. April 14, 1994: Seven top executives of major tobacco companies state, under oath, that they believe nicotine is not addictive. Tobacco industry documents suggest otherwise Documents available at The cigarette is a heavily engineered product. Designed and marketed to maximize bioavailability of nicotine and addictive potential Profits over people For decades, the tobacco industry has publicly denied the addictive nature of nicotine and the negative health effects of tobacco. On April 14, 1994, the top executives of all the major tobacco companies stated, under oath, that they believe nicotine is not addictive. Yet tobacco industry documents, which are now available publicly on the Internet ( suggest otherwise. The cigarette is a heavily-engineered product that was designed and marketed to maximize the bioavailability of nicotine and hence maximize its addictive potential. The tobacco industry is financially vested in selling its product and has taken affirmative steps to maximize profits and minimize anti-tobacco public health efforts. At times the industry has actively sought to disrupt particular public health programs and legislation, and other times it is simply trying to promote its own interests above the interests of the public health. An example of this is the development and marketing of “light” cigarettes.

An EFFECTIVE MARKETING STRATEGY: “LIGHT” CIGARETTES
The difference between Marlboro and Marlboro Lights… As smokers became more concerned about the negative health consequences of smoking, the tobacco industry created “mild,” “light,” and “ultra-light” cigarettes. These products incorporate ventilation holes on the cigarette filters in order to “reduce” the nicotine and tar yields as measured by the FTC machine-test method. During inhalation, room air is drawn through the ventilation holes into the smoke stream, diluting the amount of smoke in each puff. When “light” or “ultra-light” cigarettes are tested using a smoking machine, the yields of tar, nicotine, and carbon monoxide are significantly reduced. However, smokers do not smoke cigarettes in the same manner that the machine does. Smokers easily obstruct the ventilation holes with their lips or fingers, thereby inhaling higher amounts of tar and nicotine than might be expected based on the reported product-yield rating (machine-test yields). The actual yield of tar and nicotine for the smoker, however, might be similar or greater—depending on the smoking technique. The tobacco industry knows this but continues to market the products as if they are safer alternatives. These products often appeal to smokers who are health conscious or are thinking about quitting. However, data suggest smokers tend to compensate for reduced nicotine delivery by smoking more cigarettes per day or by smoking ‘light’ cigarettes more intensely. As a result, these products do not significantly reduce exposure to nicotine or toxins in tobacco smoke including carbon monoxide and carcinogens (Benowitz et al., 2005). This image, courtesy of Dr. Richard D. Hurt, director of the Mayo Clinic Nicotine Dependence Center - Research Program, illustrates the difference between Marlboro and Marlboro Lights. As can be appreciated from the photo, the products have cosmetic differences (white vs. brown filter-tip paper color) and an extra row of ventilation holes is found in the light version. When tested by the smoking machine, the tar and nicotine yields for Marlboro are 15 mg and 1.1 mg per cigarette, respectively. The corresponding tar and nicotine yields for Marlboro Lights are 10 mg and 0.8 mg per cigarette, respectively (FTC, 2000). Benowitz NL, Jacob P 3rd, Bernert JT, Wilson M, Wang L, Allen F, Dempsey D. (2005). Carcinogen exposure during short-term switching from regular to "light" cigarettes. Cancer Epidemiol Biomarkers Prev 14:1376–1383. Federal Trade Commission (FTC). (2000). “Tar,” Nicotine and Carbon Monoxide of the Smoke of 1294 Varieties of Domestic Cigarettes for the Year Retrieved December 31, 2006, from an extra row of ventilation holes Image courtesy of Mayo Clinic Nicotine Dependence Center - Research Program / Dr. Richard D. Hurt The Marlboro and Marlboro Lights logos are registered trademarks of Philip Morris USA.

This image depicts the marketing strategy of the tobacco industry for an ultra-light cigarette targeted toward women, a population with a lower smoking prevalence and concerns about the effect of cessation on weight gain.

TOBACCO INDUSTRY ADVERTISING
$15.15 billion spent in the U.S. in 2003 21.5% increase over 2002 figures 35.0% increase over 2001 figures Each year, the tobacco industry spends billions of dollars in promoting its products in the U.S. and abroad. This graph shows the most current data on advertising expenditures in the U.S., along with data for 1970, the first year for which these data are available in the FTC annual reports, to give a basis for comparison (FTC, 2005). Highlights of the report for 2003 are as follows: Annual spending (in the U.S. only), was $15.15 billion. The total number of cigarettes sold or given away decreased by 19.8 billion (5.1%) from 2002 to 2003. The $15.15 billion is a $2.68 billion (21.5%) increase from the $12.47 billion spent in 2002 and 125% higher than the $6.73 billion expended in 1998, when the Master Settlement Agreement went into effect. The largest category of expenditures was price discounts provided to cigarette retailers and wholesalers in order to reduce the overall price of cigarettes to consumers. This single category accounted for $10.81 billion (71.4% of total advertising and promotional expenditures). Federal Trade Commission (FTC). (2005). Cigarette Report for Retrieved December 31, 2006, from Billions of dollars spent Year Federal Trade Commission. (2005). Cigarette Report for 2003.

1932 As part of massive marketing campaigns, the tobacco industry promoted its products through trusted health professionals, including nurses.

Physicians also were central to tobacco advertising in the early to mid-1900s. It wasn’t until the 1950s that the link between smoking and cancer became public knowledge. 1936

Analysis of tobacco-industry marketing campaigns has revealed that tobacco company advertising efforts intentionally targeted the youth market (Cummings et al., 2002; Ling & Glantz, 2002). As depicted in this slide, the widely popular R. J. Reynolds “Joe Camel” ad campaign, which ran between 1988 and 1997, was specifically developed to appeal to children and adolescents. During the first three years of the Joe Camel campaign, Camel's share of the under-18 cigarette market jumped from 0.5% to 32.8%, representing a $470 million increase in annual sales for RJR Nabisco (DiFranza et al., 1991). In a study of young children, more than 90% of 6 year olds were able to correctly matched Joe Camel with a picture of a cigarette, making him as well-known as Mickey Mouse; in comparison, only 67% of adults recognized Joe Camel (Fischer et al., 1991). A recent Cochrane Database Systematic Review concluded that exposure to tobacco advertising and promotion is associated with an increased likelihood that adolescents will start to smoke. This conclusion was based on the strength of this association, the consistency of findings across observational studies, temporality of the exposure versus smoking behavior, and a theoretical plausibility for the impact of advertising on smoking behavior (Lovato et al., 2003). Cummings KM, Morley CP, Horan JK, Steger C, Leavell NR. (2002). Marketing to America's youth: Evidence from corporate documents. Tob Control 11(Suppl 1):I5–I17. DiFranza JR, Richards JW, Paulman PM, Wolf-Gillespie N, Fletcher C, Jaffe RD, Murray D. (1991). RJR Nabisco's cartoon camel promotes Camel cigarettes to children. JAMA 266:3149–3153. Fischer PM, Schwartz MP, Richards JW Jr., Goldstein AO, Rojas TH. (1991). Brand logo recognition by children aged 3 to 6 years. Mickey Mouse and Old Joe the Camel. JAMA 266:3145–3148. Ling PM, Glantz SA. (2002). Using tobacco-industry marketing research to design more effective tobacco-control campaigns. JAMA 287:2983–2999. Lovato C, Linn G, Stead L, Best A. (2003). Impact of tobacco advertising and promotion on increasing adolescent smoking behaviours. Cochrane Database Syst Rev 4:CD 1990

TOTAL: 437,902 deaths annually
ANNUAL U.S. DEATHS ATTRIBUTABLE to SMOKING, 1997–2001 Percentage of all smoking-attributable deaths* Cardiovascular diseases 137,979 Lung cancer 123,836 Respiratory diseases 101,454 Second-hand smoke* 38,112 Cancers other than lung 34,693 Other 1,828 32% 28% 23% Cigarette smoking is the primary known preventable cause of premature death in the U.S., with nearly one of every five deaths being smoking related (Mokdad, 2004). This number surpasses the combined death toll due to alcohol, car accidents, suicides, homicides, HIV disease, and illicit drug use. A total of 437,902 annual deaths due to cigarette smoking are reported by the CDC (2005) as follows: Cardiovascular disease…………137,979 Hypertension, ischemic heart disease, other heart diseases, cerebrovascular diseases, atherosclerosis, aortic aneurysm, other arterial disease Lung cancer………………………123,836 Trachea, lung, bronchus Respiratory diseases…………….101,454 Pneumonia, influenza, bronchitis, emphysema, chronic airway obstruction Second-hand smoke……………....38,112 Cancers other than lung…………..34,693 Lip, oral cavity, pharynx, esophagus, pancreas, larynx, cervix, uterus, urinary bladder, kidney, other urinary Other………………………………….1,828 *Percentages on the slide do not add to 100% due to rounding. ♪ Note to instructor(s): The Surgeon General’s Report, The Health Consequences of Involuntary Exposure to Tobacco Smoke (USDHHS, 2006) indicates that in 2005, second-hand smoke killed more than 3,000 adult nonsmokers due to lung cancer, approximately 46,000 due to coronary heart disease, and 430 newborns due to sudden infant death syndrome. Centers for Disease Control and Prevention (CDC). (2005). Annual smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 1997–2001. MMWR 54:625–628. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, JAMA 2004;291:1238–45. U.S. Department of Health and Human Services (USDHHS). (2006). The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 9% 8% <1% TOTAL: 437,902 deaths annually * In 2005, it was estimated that nearly 50,000 persons died due to second-hand smoke exposure. Centers for Disease Control and Prevention. (2005). MMWR 54:625–628.

ANNUAL SMOKING-ATTRIBUTABLE ECONOMIC COSTS—U.S., 1995–1999
Prescription drugs, $6.4 billion Other care, $5.4 billion Medical expenditures (1998) Ambulatory care, $27.2 billion Hospital care, $17.1 billion Nursing home, $19.4 billion The economic costs to society associated with smoking are enormous (CDC, 2002). In 1998, personal health-care medical expenditures attributable to smoking in the U.S. were $75.5 billion: Ambulatory care $ million Hospital care $ billion Prescription drugs $6.364 billion Nursing home care $ billion Other care $5.419 billion Total $ billion The annual smoking-attributable productivity costs (in 1995–1999) are estimated at Men $ billion Women $ billion Total $ billion Infant (neonatal) costs (not shown) are estimated at $366 million, although this value likely is understated because it does not include future medical care costs for infants affected by maternal smoking or the current costs of treating infants for conditions related to passive exposure to tobacco smoke. Grand total annual smoking-attributable economic costs for adults and infants in the United States, 1995–1999 = $ billion. This is approximately $3,391 annually for each smoker. For each pack of cigarettes sold in 1999 (approximately 22 billion sold), $3.45 was spent on medical care attributed to smoking and $3.73 in productivity losses were incurred, for a total cost of $7.18 per pack of cigarettes (CDC, 2002). Centers for Disease Control and Prevention (CDC). (2002). Annual smoking-attributable mortality, years of potential life lost, and economic costs—United States, 1995–1999. MMWR 51:300–303. Societal costs: $7.18 per pack Annual lost productivity costs (1995–1999) Men, $55.4 billion Women, $26.5 billion Billions of dollars Centers for Disease Control and Prevention. (2002). MMWR 51:300–303.

COMPOUNDS in TOBACCO SMOKE
An estimated 4,800 compounds in tobacco smoke, including 11 proven human carcinogens Gases Particles Carbon monoxide Hydrogen cyanide Ammonia Benzene Formaldehyde Nicotine Nitrosamines Lead Cadmium Polonium-210 Tobacco smoke, which is inhaled either directly or as second-hand smoke, contains an estimated 4,800 compounds. The majority of the compounds are present in the particulate phase, suspended in tobacco smoke. Based on a classification system by the International Agency for Research on Cancer, cigarette smoke contains 11 known human carcinogens (Group I), 7 probable human carcinogens (Group 2A), and 49 animal carcinogens that possibly also are carcinogens in humans (Group 2B) (NCI, 2001). Examples of detrimental compounds (some of which are carcinogens) in tobacco smoke include the following: Carbon monoxide: automobile exhaust; binds to hemoglobin, inhibits respiration Hydrogen cyanide: gas chamber poison; highly ciliotoxic, inhibits lung clearance Ammonia: floor/toilet cleaning agent; irritation of respiratory tract Nicotine : addictive substance; toxic alkaloid Benzene: solvent, banned substance in organic chemistry labs; Group I carcinogen Nitrosamines: carcinogenic in animals and probably in humans; Group 2A and 2B carcinogens Lead: heavy metal, toxic to central nervous system; Group 2B carcinogen Cadmium: heavy metal found in rechargeable batteries; Group I carcinogen Hexavalent chromium: highlighted in the movie Erin Brockovich; Group I carcinogen Arsenic: pesticide; Group I carcinogen Polonium-210: radioactive agent; Group I carcinogen Formaldehyde: embalming fluid; Group 2B carcinogen Other substances in tobacco smoke (not listed above) with sufficient evidence to be classified as Group I carcinogens in humans include 2-naphthylamine, 4-aminobiphenyl, vinyl chloride, ethylene oxide, beryllium, and nickel. ♪ Note to instructor(s): It is important to emphasize that although nicotine is the addictive component of tobacco, it does not cause the ill health effects. National Cancer Institute (NCI). (2001). Risks Associated with Low Machine-Measured Yields of Tar and Nicotine (NIH Publication No ). Smoking and Tobacco Control Monograph No. 13. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Nicotine does NOT cause the ill health effects of tobacco.

2004 REPORT of the SURGEON GENERAL: HEALTH CONSEQUENCES OF SMOKING
FOUR MAJOR CONCLUSIONS: Smoking harms nearly every organ of the body, causing many diseases and reducing the health of smokers in general. Quitting smoking has immediate as well as long-term benefits, reducing risks for diseases caused by smoking and improving health in general. Smoking cigarettes with lower machine-measured yields of tar and nicotine provides no clear benefit to health. The list of diseases caused by smoking has been expanded. In 2004, the Surgeon General published a comprehensive report detailing the health consequences of smoking. Four major conclusions of the report are as follows: 1. Smoking harms nearly every organ of the body, causing many diseases and reducing the health of smokers in general. 2. Quitting smoking has immediate as well as long-term benefits, reducing risks for diseases caused by smoking and improving health in general. 3. Smoking cigarettes with lower machine-measured yields of tar and nicotine provides no clear benefit to health. 4. The list of diseases (shown on next slide) caused by smoking has been expanded to include abdominal aortic aneurysm, acute myeloid leukemia, cataract, cervical cancer, kidney cancer, pancreatic cancer, pneumonia, periodontitis, and stomach cancer. These are in addition to diseases previously known to be caused by smoking, including bladder, esophageal, laryngeal, lung, oral, and throat cancers, chronic lung diseases, coronary heart and cardiovascular diseases, as well as reproductive effects and sudden infant death syndrome. Smoking remains the leading cause of preventable death and has negative impacts on people at all stages of life. It harms unborn babies, infants, children, adolescents, adults, and seniors. U.S. Department of Health and Human Services (USDHHS). (2004). The Health Consequences of Smoking: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. U.S. Department of Health and Human Services. (2004). The Health Consequences of Smoking: A Report of the Surgeon General.

HEALTH CONSEQUENCES of SMOKING
Cancers Acute myeloid leukemia Bladder and kidney Cervical Esophageal Gastric Laryngeal Lung Oral cavity and pharyngeal Pancreatic Pulmonary diseases Acute (e.g., pneumonia) Chronic (e.g., COPD) Cardiovascular diseases Abdominal aortic aneurysm Coronary heart disease Cerebrovascular disease Peripheral arterial disease Reproductive effects Reduced fertility in women Poor pregnancy outcomes (e.g., low birth weight, preterm delivery) Infant mortality Other effects: cataract, osteoporosis, periodontitis, poor surgical outcomes The 2004 Surgeon General’s Report on the health consequences of smoking describes a long list of diseases with sufficient evidence to infer a causal relationship with smoking. These are summarized below. Cancer Acute myeloid leukemia, bladder and kidney, cervical, esophageal, gastric, laryngeal, lung, oral cavity and pharyngeal, and pancreatic. Pulmonary Diseases Acute respiratory illnesses: Upper respiratory illnesses (rhinitis, sinusitis, laryngitis, pharyngitis) Lower respiratory illnesses (bronchitis, pneumonia) Chronic respiratory illnesses: Chronic obstructive pulmonary disease Respiratory symptoms (cough, phlegm, wheezing, dyspnea) Poor asthma control Reduced lung function Cardiovascular Diseases Abdominal aortic aneurysm, coronary heart disease (angina pectoris, ischemic heart disease, myocardial infarction), cerebrovascular disease (transient ischemic attacks, stroke), and peripheral arterial disease. Reproductive Effects Reduced fertility in women, pregnancy and pregnancy outcomes (preterm, premature rupture of membranes, placenta previa, placental abruption, pre-term delivery, low infant birth weight), infant mortality (sudden infant death syndrome) Other Effects Cataract, osteoporosis (reduced bone density in postmenopausal women, increased risk of hip fracture), periodontitis, peptic ulcer disease (in patients who are infected with Helicobacter pylori), and poor surgical outcomes (poor wound healing, respiratory complications) ♪ Note to instructor(s): For more detailed information and literature citations regarding risks for these tobacco-related illnesses, refer to the optional Pathophysiology of Tobacco-Related Disease module or the Surgeon General’s Report at U.S. Department of Health and Human Services (USDHHS). (2004). The Health Consequences of Smoking: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. U.S. Department of Health and Human Services. (2004). The Health Consequences of Smoking: A Report of the Surgeon General.

HERMAN ® is reprinted with permission from
Although the decision to use tobacco lies in the hands of each person, regulations help to determine the extent to which nonsmokers are exposed to the harms of tobacco smoke. HERMAN ® is reprinted with permission from LaughingStock Licensing Inc., Ottawa, Canada All rights reserved.

There is no safe level of second-hand smoke.
2006 REPORT of the SURGEON GENERAL: INVOLUNTARY EXPOSURE to TOBACCO SMOKE Second-hand smoke causes premature death and disease in nonsmokers (children and adults) Children: Increased risk for sudden infant death syndrome (SIDS), acute respiratory infections, ear problems, and more severe asthma There is no safe level of second-hand smoke. As noted previously, approximately 50,000 persons die annually in the United States due to second-hand smoke exposure (USDHHS, 2006). Despite the tobacco industry’s efforts to cast doubt on the link between second-hand smoke and health risks (USDHHS, 2006), few scientists and clinicians would deny that second-hand smoke is harmful. Major conclusions of the 2006 Surgeon General’s Report The Health Consequences of Involuntary Exposure to Tobacco Smoke (USDHHS, 2006) are: Second-hand smoke causes premature death and disease in children and in adults who do not smoke. Children exposed to second-hand smoke are at an increased risk for sudden infant death syndrome (SIDS), acute respiratory infections, ear problems, and more severe asthma. Smoking by parents causes respiratory symptoms and slows lung growth in their children. Exposure of adults to second-hand smoke has immediate adverse effects on the cardiovascular system and causes coronary heart disease and lung cancer. The scientific evidence indicates that there is no risk-free level of exposure to second-hand smoke. Many millions of Americans, both children and adults, are still exposed to second-hand smoke in their homes and workplaces despite substantial progress in tobacco control. Eliminating smoking in indoor spaces fully protects nonsmokers from exposure to second-hand smoke. Separating smokers from nonsmokers, cleaning the air, and ventilating buildings cannot eliminate exposures of nonsmokers to second-hand smoke. Even a little exposure is dangerous, because it alters endothelial function, immediately compromising the cardiovascular system (Otsuka et al., 2001). Otsuka R, Watanabe H, Hirata K, Tokai K, Muro T, Yoshiyama M, Takeuchi K, Yoshikawa J. (2001). Acute effects of passive smoking on the coronary circulation in healthy young adults. JAMA 286:436–441. U.S. Department of Health and Human Services (USDHHS). (2006). The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. Respiratory symptoms and slowed lung growth if parents smoke Adults: Immediate adverse effects on cardiovascular system Increased risk for coronary heart disease and lung cancer Millions of Americans are exposed to smoke in their homes/workplaces Indoor spaces: eliminating smoking fully protects nonsmokers Separating smoking areas, cleaning the air, and ventilation are ineffective USDHHS. (2006). The Health Consequences of Involuntary Exposure to Tobacco Smoke: Report of the Surgeon General.

SMOKE-FREE WORKPLACE LAWS
In recent months, there has been a substantial increase in the number of states, and countries outside of the United States (e.g., Ireland, Italy, Scotland, England, Norway, Sweden, New Zealand, Uganda, Malta, Uruguay, Hong Kong, Bhutan, and France), that have implemented new smoke-free workplace laws. This slide depicts states that have adopted statewide, smoke-free bans in offices, restaurants, and/or bars. In addition, many cities and towns have adopted local bans against smoking. ♪ Note to instructor(s): The Centers for Disease Control and Prevention has advised that people with cardiac conditions should avoid exposure to second-hand smoke because such exposure can significantly increase the risk of a myocardial infarction. This warning followed on the heels of a study reporting that the number of hospital admissions for myocardial infarction in Helena, Montana, decreased by 40% after indoor smoking was banned in the city and then returned rapidly to baseline levels when the smoking ban was overturned (Sargent et al., 2004). During the same 6 months in the years before and after the law, the average number of admissions was 40 compared with a total of 24 admissions during the 6 months in which the law was in effect. In the areas surrounding Helena, which did not enact a smoking ban, there was no appreciable change in hospital admissions for myocardial infarction. This study was published shortly before many of the states enacted smoke-free workplace laws. More recently, the Surgeon General’s Report (USDHHS, 2006) has added additional evidence in support of smoking bans in public places. ♪ Note to instructor(s): Regular updates about smoke-free workplace laws can be received by joining Joe Cherner’s listserv at Sargent R, Shepard R, Glantz S. (2004). Reduced incidence of admissions for myocardial infarction associated with public smoking ban: Before and after study. BMJ 328:977–980. U.S. Department of Health and Human Services (USDHHS). (2006). The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. Smoke-free offices, restaurants, and bars: California, Colorado, Connecticut, Delaware, Hawaii, Maine, Massachusetts, New Jersey, New York, Rhode Island, Vermont, Washington Smoke-free offices and restaurants: Arkansas, District of Columbia (bars in 2007), Florida, Georgia, Idaho, Louisiana, Montana (bars in 2009), Nevada, North Dakota, Utah (bars in 2009) Smoke-free offices: Maryland, South Dakota Data current as of November 9, 2006.

QUITTING: HEALTH BENEFITS
Time Since Quit Date Circulation improves, walking becomes easier Lung function increases up to 30% Lung cilia regain normal function Ability to clear lungs of mucus increases Coughing, fatigue, shortness of breath decrease 2 weeks to 3 months 1 to 9 months Excess risk of CHD decreases to half that of a continuing smoker The 1990 Surgeon General’s Report on the health benefits of smoking cessation outlines the numerous and substantial health benefits incurred when patients quit smoking (USDHHS, 1990): Health benefits realized 2 weeks to 3 months after quitting include the following: circulation improves, walking becomes easier, and lung function increases up to 30%. One to nine months later, lung ciliary function is restored. This improved mucociliary clearance greatly decreases the chance of infection because the lung environment is no longer as conducive to bacterial growth. Consequently, coughing, sinus congestion, fatigue, and shortness of breath decrease. In some patients, coughing might actually increase shortly after quitting. This is because the cilia in pulmonary epithelial cells are functioning “normally” and are more effectively clearing the residual tars and other accumulated components of tobacco smoke. One year later, excess risk of coronary heart disease (CHD) is decreased to half that of a smoker. After 5 to 15 years, stroke risk is reduced to a rate similar to that of people who have never smoked. Ten years after quitting, an individual’s chance of dying of lung cancer is approximately half that of continuing smokers. Additionally, the chance of getting mouth, throat, esophagus, bladder, kidney, or pancreatic cancer is decreased. Finally, 15 years after quitting, an individual’s risk of CHD is reduced to a rate similar to that of people who have never smoked. Thus the benefits of quitting are significant. It is never too late to quit to incur many of the benefits of quitting. The next two slides depict some advantages of quitting earlier in life, as opposed to later. U.S. Department of Health and Human Services (USDHHS). (1990). The Health Benefits of Smoking Cessation. A Report of the Surgeon General (DHHS Publication No. CDC ). U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention and Health Promotion, Office on Smoking and Health. 1 year Risk of stroke is reduced to that of people who have never smoked 5 years Lung cancer death rate drops to half that of a continuing smoker Risk of cancer of mouth, throat, esophagus, bladder, kidney, pancreas decrease 10 years Risk of CHD is similar to that of people who have never smoked after 15 years

BENEFICIAL EFFECTS of QUITTING: PULMONARY EFFECTS
AT ANY AGE, there are benefits of quitting. Never smoked or not susceptible to smoke 100 75 This graph (Fletcher & Peto, 1977) shows measurable improvements in lung function as a result of quitting. Forced expiratory volume (FEV1) falls gradually with age; for the majority of nonsmokers and many smokers, clinically significant FEV1 reduction does not occur. However, in susceptible individuals, smoking causes irreversible obstructive damage to the respiratory system. If a susceptible smoker quits smoking at age 45 years, he or she likely will regain a substantial proportion of potentially lost FEV1. Less substantial, but still visible, benefits of quitting can be seen among persons who quit even at a much older age (65 years). Fletcher C, Peto R. (1977). The natural history of chronic airflow obstruction. Br Med J 1(6077):1645–1648. Stopped smoking at 45 (mild COPD) Smoked regularly and susceptible to effects of smoke FEV1 (% of value at age 25) 50 Disability 25 Stopped smoking at 65 (severe COPD) Death 25 50 75 Age (years) COPD = chronic obstructive pulmonary disease Reprinted with permission. Fletcher & Peto. (1977). BMJ 1(6077):1645–1648.

Reduction in cumulative risk of death from lung cancer in men
Age in years Reduction in cumulative risk of death from lung cancer in men Despite the detrimental effects of tobacco on pulmonary health, smoking cessation can lead to a significant reduction in the cumulative risk of death from lung cancer. This graph demonstrates the risk of lung cancer mortality incurred by men at age 75; the risk estimates are 15.9% for those who do not quit smoking cigarettes and 9.9%, 6.0%, 3.0%, and 1.7% for men who stopped at ages 60, 50, 40, and 30, respectively (Peto et al., 2000). Similar trends are seen for women. These aggregate data suggest that quitting, at any age, reduces the risk of death from lung cancer. Peto R, Darby S, Deo H, Silcocks P, Whitley E, Doll R. (2000). Smoking, smoking cessation, and lung cancer in the UK since 1950: Combination of national statistics with two case-control studies. BMJ 321(7257):323–329. Reprinted with permission. Peto et al. (2000). BMJ 321(7257):323–329.

SMOKING CESSATION: REDUCED RISK of DEATH
Prospective study of 34,439 male British doctors Mortality was monitored for 50 years (1951–2001) On average, cigarette smokers die approximately 10 years younger than do nonsmokers. Perhaps one of the greatest tobacco studies of all times is a prospective cohort of British male doctors (Doll et al., 2004). This study was conducted by Oxford University Professor Richard Doll, a leading cancer epidemiologist, who more than 50 years ago first reported that smoking causes lung cancer. Recent findings show a clear picture of the risks associated with smoking. Doll and colleagues compared the hazards of cigarette smoking in men who formed their smoking habits at different periods, and the extent of the reduction in risk when cigarette smoking was stopped at different ages. Quitting at ages 30, 40, 50, and 60 resulted in 10, 9, 6, and 3 years of life gained, respectively. On average, cigarette smokers die approximately 10 years younger than do nonsmokers, and of those who continue smoking, at least half will eventually die due to a tobacco-related disease. Persons who quit before age 35 add 10 years of life and have a life expectancy similar to men who had never smoked. ♪ Note to instructor(s): The number of years of life saved by quitting varies across studies. For example, in a CDC report (2002), it was shown that the average number of years of life lost because of smoking was 13.2 years for male smokers and 14.5 years for female smokers. ♪ Note to instructor(s): Sir Richard Doll passed away on Sunday July 24, He was the foremost epidemiologist of the twentieth century and is best known for his research establishing the correlation between smoking and lung cancer. “It is a rare occasion when a researcher can, within the course of his or her own lifetime, both open and close the book on a research question of such profound public health importance as the link between smoking and cancer. Sir Richard Doll's pioneering research has, perhaps more so than any other epidemiologist of his time, altered the landscape of disease prevention and consequently saved millions of lives worldwide.” -- KS Hudmon, Centers for Disease Control and Prevention (CDC). (2002). Annual smoking-attributable mortality, years of potential life lost, and economic costs—United States, 1995–1999. MMWR 51:300–303. Doll R, Peto R, Boreham J, Sutherland I. (2004). Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ 328(7455):1519–1527. Years of life gained Among those who continue smoking, at least half will die due to a tobacco-related disease. Age at cessation (years) Doll et al. (2004). BMJ 328(7455):1519–1527.

FINANCIAL IMPACT of SMOKING
Buying cigarettes every day for 50 $4.26 per pack Money banked monthly, earning 1.5% interest $342,729 In addition to the many health benefits of quitting, there are financial benefits associated with quitting. The financial costs of tobacco use can be substantial to a smoker, particularly when costs are accrued over a lifetime. What three levels of smokers who buy cigarettes every day for 50 years at $4.26 per pack (average national cost; Campaign for Tobacco-Free Kids, 2006) will have if they instead bank their cigarette money each month:1 1 pack a day: $114,243 2 packs a day: $228,486 3 packs a day: $342,729 Even if you don’t invest the money, the savings associated with not smoking is more than $1,500 a year for a pack-a-day smoker. Assumes constant price per pack, an annual interest rate of 1.5% (not adjusted for inflation), and that the money was banked monthly. Savings calculator tool available at Campaign for Tobacco-Free Kids. (2006). “State Cigarette Excise Tax Rates & Rankings.” Retrieved December 31, 2006, from $228,486 Packs per day $114,243 100 200 300 400 Hundreds of thousands of dollars lost

EPIDEMIOLOGY of TOBACCO USE: SUMMARY
About one in five adults are current smokers; smoking prevalence varies by sociodemographic characteristics. Nearly half a million U.S. deaths are attributable to smoking annually. Smoking costs the U.S. $157.7 billion per year. Lifetime financial costs of smoking can exceed $300,000 for a heavy smoker. At any age, there are benefits to quitting smoking. The biggest opponent to tobacco control efforts is the tobacco industry itself. To summarize: About one in five U.S. adults smoke. Nearly half a million U.S. deaths are attributable to smoking annually. Smoking costs the U.S. approximately $157.7 billion per year. For the individual, a lifetime of heavy smoking can cost more than $300,000. There are benefits to quitting smoking at any age. The biggest opponent to tobacco control efforts is the tobacco industry itself. Thus, it is clear that tobacco use is a significant public health problem. The morbidity and mortality associated with tobacco use can be curbed through effective tobacco prevention and cessation efforts.

FORMS of TOBACCO This module focuses on different forms of tobacco that are available in the U.S.

FORMS of TOBACCO Cigarettes Spit tobacco (chewing tobacco, oral snuff)
Pipes Cigars Clove cigarettes Bidis Waterpipes (e.g., hookah) Many forms of tobacco are available in the U.S.: Cigarettes Spit tobacco (chewing tobacco and oral snuff) Pipes Cigars Clove cigarettes Bidis Waterpipes (e.g., hookah, shisha, narghile, goza, hubble bubble) Several of these forms, such as clove cigarettes, bidis, and hookah, have attained increased popularity in recent years. Image courtesy of the Centers for Disease Control and Prevention / Rick Ward

CIGARETTES Most common form of tobacco used in U.S.
376 billion cigarettes consumed in 2005 Per-capita consumption was 1,716 in 2005 U.S. smokers consumed an estimated 376 billion cigarettes in Although this value is approximately 3% less than the previous year, cigarettes are, by far, the most common form of tobacco used in the U.S. (USDA, 2006). Per-capita consumption in 2005 for adults aged 18 years or older was estimated at 1,716 cigarettes (USDA, 2006). U.S. Department of Agriculture (USDA), Economic Research Service. (2006, April 28). Tobacco Outlook. Report TBS-260. Retrieved May 9, 2006, from

AMERICAN CIGARETTES Sold in packs (20 cigarettes/pack)
Total nicotine content (per cigarette) Average 10.2 mg (range 7.2 to 13.4 mg) Average machine yield (per cigarette) Nicotine 0.88 mg (range <0.05 to 2.0 mg) Tar 12 mg (range <0.5 to 27 mg) Low tar/nicotine cigarettes Actual exposure may be higher Not safer In the U.S., cigarettes are generally sold in packs containing 20 cigarettes, and a carton of cigarettes generally contains 10 packs. In a study analyzing 32 of the top-selling American brands of cigarettes, the total nicotine content per cigarette averaged 10.2 mg with a range of 7.2 to 13.4 mg (Kozlowski et al., 1998). Notably, this study analyzed regular, light, and ultra-light cigarettes. Thus cigarettes labeled as “light” or “ultra-light” are not necessarily low nicotine content cigarettes. Cigarette ratings for tar and nicotine are determined by a standardized U.S. Federal Trade Commission machine testing procedure that involves inhalation of 35 mL of smoke over 2 seconds every 60 seconds. Under these conditions, in 1998 the average machine yield of nicotine per American cigarette was 0.88 mg (range <0.05 to 2.0 mg); tar yields per cigarette averaged 12 mg (range <0.5 to 27 mg) (FTC, 2000). Full-flavor brands have higher nicotine and tar yields compared to light or ultra-light brands. For example, based on the FTC method, the tar and nicotine yields for Marlboro Full Flavor are 15 mg and 1.1 mg per cigarette, respectively. The corresponding tar and nicotine yields for Marlboro Light are 10 mg and 0.8 mg per cigarette, respectively (FTC, 2000). ♪ Note to instructor(s): A report issued by the Massachusetts Tobacco Control Program in 2006 has revealed that American tobacco manufacturers (Lorillard, Philip Morris, and RJ Reynolds) have increased the total nicotine content of cigarettes over a 6-year time period by nearly 17% (from an average of 12.9 mg per cigarette in 1998 to 14.3 mg per cigarette in 2004). This significant increase in tobacco content has lead to a nearly 10% increase in nicotine yield per cigarette during the same time period (from 1.72 mg in 1998 to 1.89 mg in 2004) (Keithly et al., 2006). Federal Trade Commission (FTC). (2000). “Tar,” Nicotine and Carbon Monoxide of the Smoke of 1294 Varieties of Domestic Cigarettes for the Year Retrieved May 8, 2006, from Keithly L, Cullen D, Land T. Changes in Nicotine Yield: 1998– Report produced by the Massachusetts Tobacco Control Program, Massachusetts Department of Public Health. Retrieved December 8, 2006, from Kozlowski LT, Mehta NY, Sweeney CT, Schwartz SS, Vogler GP, Jarvis MJ, West RJ. (1998). Filter ventilation and nicotine content of tobacco in cigarettes from Canada, the United Kingdom, and the U.S. Tob Control 7:369–375. Marlboro and Marlboro Light are registered trademarks of Philip Morris, Inc.

SPIT TOBACCO Chewing tobacco Snuff Looseleaf Plug Twist Moist Dry
The use of spit tobacco products in the U.S. was widespread until the end of the 19th century. With the advent of antispitting laws, loss of social acceptability, and increased popularity of cigarette smoking, its use declined rapidly in the 20th century. However, national data indicate a resurgence in spit tobacco use, particularly among young males (Ebbert et al., 2004). Spit tobacco is classified as either chewing tobacco or snuff (USDHHS, 1986). Chewing tobacco is chewed or held in the cheek or lower lip. The following types of chewing tobacco are marketed in the U.S.: Looseleaf: consists of stripped and processed tobacco leaves that are stemmed, cut, and loosely packed to form small strips of shredded tobacco (depicted in slide). Most brands are sweetened and flavored with licorice. Generally available in a 3-ounce pouch. Users tuck a piece of tobacco ¾ to 1 inch in diameter in the back of the mouth between the gum and jaw and chew intermittently. Plug: made from tobacco leaves or fragments wrapped in fine tobacco and pressed into bricks (depicted in slide). Most plug tobacco is sweetened and flavored with licorice. Generally available in compressed bricks or blocks. Users chew or hold a piece inside cheek or lower lip. Twist: handmade from leaf tobacco treated with a tar-like tobacco leaf extract and twisted into strands (depicted in slide) that are dried. Usually contains no sweeteners or flavoring agents. Generally sold by the piece. Used in a manner similar to plug tobacco. Snuff has a much finer consistency than chewing tobacco and is held in place in the mouth without chewing. The following types of snuff are marketed in the U.S.: Moist snuff: consists of tobacco stems and leaves that are processed into fine particles, strips, or mini-sachets resembling tea bags (depicted in slide). Some products are flavored. Has moisture content of up to 50%. Available in cans and plastic containers. Users place a small amount (a “pinch”) between the lip or cheek and gum (also known as dipping) and suck on the moist mass of tobacco for 30 minutes or longer. Because of increased surface area, finer cuts of tobacco result in more rapid absorption of nicotine. Dry snuff: consists of tobacco that is fermented and processed into a dry powdered form. Generally has a moisture content of less than 10%. Available in cans and glass containers. Used in a manner similar to moist snuff but also may be sniffed. Ebbert JO, Carr AB, Dale LC. (2004). Smokeless tobacco: An emerging addiction. Med Clin N Am 88:1593–1605. U.S. Department of Health and Human Services (USDHHS). (1986). The Health Consequences of Using Smokeless Tobacco. A Report of the Advisory Committee to the Surgeon General (NIH Publication No ). Retrieved May 8, 2006, from The Copenhagen and Skoal logos are registered trademarks of U.S. Smokeless Tobacco Company, and Red Man is a registered trademark of Swedish Match.

SPIT TOBACCO: U.S. OUTPUT, 1950–2005
This graph depicts the output (in millions of pounds) of spit tobacco products in the U.S. from 1950 to 2005. Consumption of chewing tobacco (looseleaf, plug, and twist) has been on the decline since the mid-1980s (USDA, 2006). In contrast, snuff production has been increasing steadily since the late 1980s. In 2005, snuff consumption increased by an estimated 2% from the previous year (USDA, 2006). Snuff usage might be increasing as consumers substitute spit tobacco for cigarettes in situations where smoking is restricted or prohibited. U.S. Department of Agriculture (USDA), Market and Trade Economics Division, Economic Research Service. (2004, December). Tobacco Situation and Outlook Yearbook. Report TBS Retrieved May 9, 2006, from U.S. Department of Agriculture (USDA), Economic Research Service. (2006, April 28). Tobacco Outlook. Report TBS-260. Retrieved May 9, 2006, from Graph based on data from U.S. Department of Agriculture. Tobacco Situation and Outlook Yearbook TBS-2004 (2004) and Tobacco Outlook TBS-260 (2006).

SPIT TOBACCO Estimated 7.2 million users in the U.S. in 2004
Males (6.2%) more likely than females (0.5%) to be current users Prevalence highest among Young adults aged years American Indians and Alaskan Natives Residents of the southern U.S. and rural areas Significant health risks Numerous carcinogens Nicotine exposure comparable to that of smokers, leading to Physical dependence Withdrawal symptoms after abstinence According to the U.S. Department of Health and Human Services, in 2004 an estimated 7.2 million Americans aged 12 years or older (3.0%) had used spit tobacco in the past month. Males (5.8%) were more likely than females (0.3%) to be current users (USDHHS, 2005). The prevalence of spit tobacco use is highest among individuals aged 18–25 years and is substantially higher among American Indians, Alaskan Natives, and residents of the southern U.S. and rural areas (Ebbert et al., 2004; USDHHS, 2005). Users of spit tobacco often believe this is a safe alternative to smoking cigarettes, because it is not inhaled. This is not true. Spit tobacco has high concentrations of numerous carcinogens, including nitrosamines, polycyclic aromatic hydrocarbons, and radioactive polonium-210, which are in direct contact with mucosal tissues for prolonged periods (USDHHS, 1986). Furthermore, regular spit tobacco users experience comparable exposure to nicotine and are as likely to develop physical dependence as are regular smokers (Ebbert, 2004). ♪ Note to instructor(s): Additional data, provided by the Centers for Disease Control and Prevention (CDC, 2006), indicate that in 2005, 2.3% of the adult population (ages 18 and older) had used chewing tobacco or snuff at least 20 times during their lifetimes and reported using chewing tobacco or snuff every day or some days. The prevalence is higher among men (4.5%) than among women (0.2%). Centers for Disease Control and Prevention. (2006). Tobacco use among adults—United States, MMWR 55:1145–1147. Ebbert JO, Carr AB, Dale LC. (2004). Smokeless tobacco: An emerging addiction. Med Clin N Am 88:1593–1605. U.S. Department of Health and Human Services (USDHHS) The Health Consequences of Using Smokeless Tobacco. A Report of the Advisory Committee to the Surgeon General (NIH Publication No ). Retrieved December 31, 2006, from U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration. (2005). Results from the 2004 National Survey on Drug Use and Health: National Findings (Office of Applied Studies, NHSDA Series H-28, DHHS Publication No. SMA 05–4062). Retrieved December 31, 2006 from

NICOTINE CONTENT in SPIT TOBACCO PRODUCTS
Dose Product pH Total free nicotine (mg/g) Low Skoal Bandits Wintergreen 6.9 0.5 Medium Skoal Long Cut Wintergreen 7.4 2.0 Medium-High Original Fine Cut Skoal Wintergreen 7.6 2.9 High Copenhagen Snuff 8.6 9.0 This slide presents the nicotine content of some commonly used spit tobacco products (Henningfield et al., 1995). Absorption of nicotine from chewing tobacco and snuff is pH dependent. With increasing pH, the fraction of free (un-ionized) nicotine increases, leading to increased absorption of nicotine across the buccal mucosa. Spit tobacco manufacturers manipulate the nicotine content and pH of their products by adding alkaline buffering agents and changing the tobacco processing methods to control the delivery of nicotine (Ebbert et al., 2004). For example, a “starter” formulation, such as Skoal Bandits, is more acidic (pH=6.9) and has a lower percentage of free nicotine to increase tolerability. Once dependence has been established, users generally advance to more alkaline, higher free nicotine content products such as Skoal Fine Cut (pH=7.6) and Copenhagen (pH=8.6), which are capable of delivering higher levels of nicotine. Under standardized laboratory conditions, the observed peak plasma levels of nicotine were 4.6 times higher with Copenhagen than with Skoal Bandits (Fant et al., 1999). Ebbert JO, Carr AB, Dale LC. (2004). Smokeless tobacco: An emerging addiction. Med Clin N Am 88:1593–1605. Fant RV, Henningfield JE, Nelson RA, Pickworth WB. (1999). Pharmacokinetics and pharmacodynamics of moist snuff in humans. Tob Control 8:387–392. Henningfield JE, Radzius A, Cone EJ. (1995). Estimation of available nicotine content of six smokeless tobacco products. Tob Control 4:57–61. Dose Product pH Total Free Nicotine (mg/g) Free Nicotine (%) Low Skoal Bandits Wintergreen 6.9 0.5 7.1 Medium Skoal Long Cut Wintergreen 7.4 2.0 19.4 Medium-High Original Fine Cut Skoal Wintergreen 7.6 2.9 27.6 High Copenhagen Snuff 8.6 9.0 79.2 Data from Henningfield et al. (1995). Tob Control 4:57–61.

HEALTH CONSEQUENCES of SPIT TOBACCO USE
Periodontal effects Gingival recession Bone attachment loss Dental caries Oral leukoplakia Cancer Oral cancer Pharyngeal cancer ♪ Note to instructor(s): Please delete this slide if you are also teaching the Epidemiology of Tobacco Use module. Like smoking, chewing and dipping have serious health effects (Ebbert et al., 2004; Taybos, 2003), including the following: Periodontal effects: Regular users of spit tobacco are at significant risk for the development of gingival recession (complete or partial loss of the tissue covering the root of the tooth) and periodontal degeneration. The loss of gingival tissue generally occurs at sites constantly exposed to tobacco. The high sugar content found in many spit tobacco products might account for the increased incidence of dental caries in spit tobacco users. Soft tissue alterations/leukoplakia: Oral leukoplakia is the main precancerous effect of spit tobacco for which the health care provider should screen. These light-colored lesions are formed in the mouth through contact between tobacco and the soft tissues of the inner mouth. Continued use can transform these lesions into carcinomas. When users quit, the oral leukoplakia tends to disappear. Cancer: The most serious consequence of spit tobacco use is an increased risk for the development of oral and pharyngeal cancers. The nitrosamine levels of moist snuff are very high; most oral cancers are caused by the use of moist snuff. Use of alcohol further increases risk of oral cancer. Counseling can be used successfully for spit tobacco cessation; pharmacotherapy might be helpful in some cases, although the effects with spit tobacco users are not well established. Ebbert JO, Carr AB, Dale LC. (2004). Smokeless tobacco: An emerging addiction. Med Clin N Am 88:1593–1605. Taybos G. (2003). Oral changes associated with tobacco use. Am J Med Sci 326:179–182. Oral Leukoplakia Image courtesy of Dr. Sol Silverman - University of California San Francisco

PIPE TOBACCO Prevalence of pipe smoking in the U.S. is less than 1%
Pipe smokers have an increased risk of death due to: Cancer (lung, oral cavity, esophagus, larynx) Chronic obstructive pulmonary disease Risk of smoking tobacco-related death: cigarettes > pipes ≈ cigars The consumption of loose tobacco (smoking tobacco) for pipes has been in steady decline over the past fifty years (USDA, 2004). Data from the National Survey on Drug Use and Health in 2003 suggest the prevalence of pipe smoking among Americans is less than 1% (USDHHS, 2004). Compared to never-smokers, pipe smokers have an increased risk of death from lung, oral, esophageal, and laryngeal cancer and chronic obstructive pulmonary disease (Henley et al., 2004). The risk of tobacco-related mortality among pipe smokers is lower than that observed in cigarette smokers and comparable to that found among cigar smokers (Henley et al., 2004). These differences might result from the tendency of pipe and cigar smokers to smoke less and generally to inhale less deeply than do cigarette smokers. Henley SJ, Thun MJ, Chao A, Calle EE. (2004). Association between exclusive pipe smoking and mortality from cancer and other diseases. J Natl Cancer Inst 96:853–861. U.S. Department of Agriculture (USDA), Market and Trade Economics Division, Economic Research Service. (2004, December). Tobacco Situation and Outlook Yearbook. Report TBS Retrieved May 8, 2006, from U.S. Department of Health and Human Services (USDHHS), Substance Abuse and Mental Health Services Administration. (2004). Results from the 2003 National Survey on Drug Use and Health: National Findings (Office of Applied Studies, NHSDA Series H-25, DHHS Publication No. SMA 04–3964). Retrieved May 8, 2006, from

Since the early 1990s, sales of cigars in the U.S. have increased markedly due to the perception that cigar smoking is a symbol of wealth and success and the mistaken impression that they are a safe alternative to cigarettes (Nyman et al., 2002). Nyman AL, Taylor TM, Biener L. (2002). Trends in cigar smoking and perceptions of health risks among Massachusetts adults. Tob Control 11(Suppl 2):ii25–ii28. HERMAN ® is reprinted with permission from LaughingStock Licensing Inc., Ottawa, Canada All rights reserved.

CIGARS Estimated 13.7 million cigar smokers in the U.S. in 2004
Tobacco content of cigars varies greatly One cigar can deliver enough nicotine to establish and maintain dependence Cigar smoking is not a safe alternative to cigarette smoking Cigars are conventionally defined as “any roll of tobacco wrapped in leaf tobacco or in any substance containing tobacco” (Baker et al., 2000). Cigar tobacco is generally air cured and produces smoke with a more alkaline pH, which allows for buccal absorption of nicotine. According to the U.S. Department of Health and Human Services, in 2004 an estimated 13.7 million Americans aged 12 years or older (5.7%) had smoked one or more cigars in the past month (USDHHS, 2005). The prevalence of cigar use was highest among individuals aged years (12.7%); males (9.8%) were more likely than females (1.9%) to be current cigar smokers (USDHHS, 2005). Exactly how much nicotine an individual might obtain from a single cigar is difficult to determine or generalize, because cigar weight and nicotine content vary widely from brand to brand and from cigar to cigar. Most cigars range in weight from about 1 to 22 g; a typical cigarette weighs less than 1 g. The nicotine content in 10 commercially available cigars studied in 1996 ranged from 10 to 444 mg (Henningfield et al., 1999). In comparison, standard U.S. cigarettes have a relatively narrow total nicotine content, ranging between 7.2 and 13.4 mg of nicotine per cigarette (Kozlowski et al., 1998). Relating these data, Henningfield and colleagues concluded that it is possible for one large cigar to contain as much tobacco as an entire pack of cigarettes and deliver enough nicotine to establish and maintain dependence (Henningfield et al., 1999). Cigar smoking is not a safe alternative to cigarette smoking. The adverse health effects of cigar smoking have been well described and include an increased risk of cancer of the lung, oral cavity, larynx, esophagus, and pancreas. In addition, cigar smokers who inhale deeply are at increased risk for developing cardiovascular disease and chronic obstructive pulmonary disease (Baker et. al., 2000; NCI, 1998). On average, cigarette smokers who switch to smoking only cigars will decrease their risk of developing lung cancer, but their risk remains markedly higher than if they were to quit smoking altogether (NCI, 1998). ♪ Note to instructor(s): Additional data, provided by the Centers for Disease Control and Prevention (CDC, 2006), indicate that in 2005, 2.2% of the adult population (ages 18 and older) had smoked at least 50 cigars in their lifetime and reported smoking cigars every day or some days. The prevalence is higher among men (4.3%) than among women (0.3%). Baker F, Ainsworth SR, Dye JT, Crammer C, Thun MJ, et al. (2000). Health risks associated with cigar smoking. JAMA 284:735–740. Centers for Disease Control and Prevention. (2006). Tobacco use among adults—United States, MMWR 55:1145–1147. Henningfield JE, Fant RV, Radzius A, Frost S. (1999). Nicotine concentration, smoke pH, and whole tobacco aqueous pH of some cigar brands and types popular in the U.S. Nicotine Tob Res 1:163–168. Kozlowski LT, Mehta NY, Sweeney CT, Schwartz SS, Vogler GP, Jarvis MJ, West RJ. (1998). Filter ventilation and nicotine content of tobacco in cigarettes from Canada, the United Kingdom, and the U.S.. Tob Control 7:369–375. National Cancer Institute (NCI). (1998). Cigars: Health Effects and Trends (Smoking and Tobacco Control Monograph No. 9; NIH Publication No ). Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, p. 67. U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration. (2005). Results from the 2004 National Survey on Drug Use and Health: National Findings (Office of Applied Studies, NHSDA Series H-28, DHHS Publication No. SMA 05–4062). Retrieved August 10, 2006 from

CIGARS: U.S. CONSUMPTION, 1950–2005
As depicted in this graph, cigar consumption in the U.S. has increased significantly over the past decade. (USDA, 2004, 2006). According to the U.S. Department of Agriculture Economic Research Service, cigar consumption reached an estimated 5.1 billion in 2005 (USDA, 2006). Some data suggest the increased consumption is due to a greater prevalence of occasional cigar smoking by previous nonsmokers, particularly among those of higher socioeconomic status (NCI, 1998). This trend is likely the result of enhanced marketing and promotional efforts by the tobacco industry. For example, cigar advertisements often depict celebrities or athletes, associating cigar smoking with glamour, affluence, and success. Similarly, popular magazines including Cigar Aficionado and Smoke overtly promote cigar use and repeatedly reinforce the concept that cigar smoking is synonymous with a successful lifestyle (Wenger et al., 2001). Increasing numbers of former cigarette smokers switching to cigars and experimentation among adolescents with cigar smoking might also play a role in the increased prevalence of cigar use (NCI, 1998). National Cancer Institute (NCI). (1998). Cigars: Health Effects and Trends (Smoking and Tobacco Control Monograph No. 9; NIH Publication No ). Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. U.S. Department of Agriculture (USDA), Market and Trade Economics Division, Economic Research Service. (2004, December). Tobacco Situation and Outlook Yearbook. Report TBS Retrieved May 9, 2006, from U.S. Department of Agriculture (USDA), Economic Research Service. (2006, April 28). Tobacco Outlook. Report TBS-260. Retrieved May 9, 2006, from Wenger LD, Malone RE, George A, Bero LA. (2001). Cigar magazines: Using tobacco to sell a lifestyle. Tob Control 10:279–284. Graph based on data from U.S. Department of Agriculture. Tobacco Situation and Outlook Yearbook TBS-2004 (2004) and Tobacco Outlook TBS-260 (2006).

CLOVE CIGARETTES (also known as KRETEKS)
Mixture of tobacco and cloves Imported from Indonesia Use is more prevalent among young smokers Two times the tar and nicotine content of standard cigarettes Clove cigarettes or “kreteks” have been imported into the U.S. from Indonesia since the late 1960s. Clove cigarettes contain approximately 60–70% tobacco and 30–40% minced cloves (AMA, 1988). In Indonesia, where these products originate, smokers typically do not inhale. In contrast, the typical clove cigarette smoker in the U.S. (aged 17–30 years) inhales deeply and retains the smoke in the lungs, subsequently increasing the risk for potentially harmful effects. In smoking machine tests, clove cigarettes deliver nearly twice as much nicotine and carbon monoxide and nearly three times as much tar as conventional filtered U.S. cigarettes (Malson et al., 2003). ♪ Note to instructor(s): Clove cigarettes are tobacco products, and smoking them carries all the hazards associated with smoking all-tobacco cigarettes. In addition, the smoking of clove cigarettes has been associated with rare but serious cases of hemorrhagic pulmonary edema, pneumonia, bronchitis, and hemoptysis (AMA, 1988; CDC, 1985; Guidotti et al., 1989). It has been speculated that eugenol, a compound possessing local anesthetic properties and present in large quantities in clove cigarette smoke, might be toxic to pulmonary tissue. The anesthetic effects of eugenol also might increase the risk of pulmonary aspiration resulting from an impaired gag reflex (Guidotti et al., 1989). Clove cigarettes also contain flavoring compounds that exceed those present in standard cigarettes. The health impact of these flavoring compounds currently is not known (Stanfill et al., 2006). American Medical Association (AMA) Council on Scientific Affairs. (1988). Council report: Evaluation of the health hazard of clove cigarettes. JAMA 260:3641–3644. Centers for Disease Control and Prevention (CDC). (1985). Epidemiologic notes and reports illnesses possibly associated with smoking clove cigarettes. MMWR 34:297–299. Guidotti TL, Laing L, Prakash U. (1989). Clove cigarettes: The basis for concern regarding health effects. West J Med 151:220–228. Malson JL, Lee EM, Murty R, Moolchan ET, Pickworth WB. (2003). Clove cigarette smoking: Biochemical, physiological, and subjective effects. Pharmacol Biochem Behav 74:739–745. Stanfill SB, Brown CR, Yan X, Watson CH, Ashley DL. (2006). Quantification of flavor-related compounds in the unburned contents of bidi and clove cigarettes. J Agric Food Chem 54:8580–8588.

BIDIS Imported from India Resemble marijuana joints
Available in candy flavors Deliver higher levels of tar, carbon monoxide, and nicotine than cigarettes “Cigarettes with training wheels” Bidis are small, brown, hand-rolled cigarettes imported primarily from India and other Southeast Asian countries; they consist of tobacco wrapped in a tendu or temburni leaf (CDC, 1999). Bidis resemble marijuana joints, which may impart a counterculture attraction. Bidis, which are available in chocolate, vanilla, strawberry, cherry, mango, orange, and other flavors, tend to be popular among younger smokers. In a recent survey of 63,728 adults in 15 U.S. states, young adults (18-24 years) reported the highest rates of ever (16.5%) and current (1.4%) bidi use. Among young adults, males, blacks and current cigarette smokers were more likely to have ever tried or be current bidi users (Delnevo et al., 2004). In a previous survey in Massachusetts, reasons cited by urban adolescents for smoking bidis were that they were better tasting, less expensive, safer, and easier to buy than traditional cigarettes (CDC, 1999). Although bidis contain less tobacco than standard cigarettes, studies have shown they produce substantial amounts of tar, nicotine, and carbon monoxide (CDC 1999; Rickert, 1999; Watson et al., 2003). A study using standardized smoking machine testing methods found that bidis deliver three times the amount of carbon monoxide and nicotine and nearly five times the amount of tar found in standard cigarettes (Rickert, 1999). Because of the low combustibility of the leaf wrapper, bidis must be puffed constantly to keep them lit. As a result, bidi smokers inhale more frequently and more deeply, thereby markedly increasing the delivery of tar and other toxins (CDC, 1999). Most bidis do not have a traditional filter tip, which further increases exposure to toxic constituents present in smoke. Like clove cigarettes, bidis also contain flavoring compounds that exceed those present in standard cigarettes. The health impact of these flavoring compounds currently is not known (Stanfill et al., 2006). Spot checks in various retail outlets have shown that many of these products are not labeled with health warnings (Taylor & Biener, 2001). The absence of Surgeon General warning labels might lead to the false impression that these products are safer than other forms of tobacco. Experts have referred to these forms of tobacco as “cigarettes with training wheels,” because young smokers become addicted to the nicotine in these candy-flavored cigarettes, later transferring their addiction to more conventional tobacco formulations (clove cigarettes, cigarettes, spit tobacco). Centers for Disease Control and Prevention (CDC). (1999). Bidi use among urban youth—Massachusetts, March–April MMWR 48:796–799. Delnevo CD, Pevzner ES, Hrywna M, Lewis MJ. (2004). Bidi cigarette use among young adults in 15 states. Prev Med 39:207–211. Rickert WS. (1999). Determination of Yields of “Tar", Nicotine and Carbon Monoxide from Bidi Cigarettes: Final Report. Ontario, Canada: Labstat International, Inc. Stanfill SB, Brown CR, Yan X, Watson CH, Ashley DL. (2006). Quantification of flavor-related compounds in the unburned contents of bidi and clove cigarettes. J Agric Food Chem 54:8580–8588. Taylor TM, Biener L. (2001). Bidi smoking among Massachusetts teenagers. Prev Med 32:89–92. Watson CH, Polzin GM, Calafat AM, Ashley DL. (2003). Determination of tar, nicotine, and carbon monoxide yields in the smoke of bidi cigarettes. Nicotine Tob Res 5:747–753. Image courtesy of the Centers for Disease Control and Prevention / Dr. Clifford H. Watson

BIDIS This photo, provided by the Centers for Disease Control and Prevention, demonstrates differences in the tobacco within a bidi (top) and a cigarette (bottom). Note that although bidis might contain less tobacco, because of their unique composition they deliver higher levels of tar, carbon monoxide, and nicotine than do standard U.S. cigarettes. Image courtesy of the Centers for Disease Control and Prevention / Dr. Clifford H. Watson

WATERPIPES Also known as Hookah Shisha Narghile Goza Hubble bubble
Tobacco flavored with fruit pulp, honey, and molasses Increasingly popular among young smokers in coffee houses, bars, and lounges The waterpipe is an ancient smoking apparatus whereby users inhale smoke that is passed through water. Waterpipe nomenclature is region-specific and includes names such as “hookah” (Africa and Indian subcontinent), “narghile” [nar-gee-leh], “nargile” (Israel, Jordan, Lebanon, Syria), “shisha”, “boory” or “goza” (Egypt, Saudi Arabia) and “hubble bubble” (many regions) (Maziak et al., 2004). The waterpipe consists of the following major components: Head: located at the top of the waterpipe; generally constructed of clay. Tobacco is placed in the head and then covered with perforated aluminum foil. Small pieces of burning charcoal are placed on top of the foil. Heat emanating from the burning charcoal is drawn through the tobacco mixture, which then generates smoke. Body: the section between the head and water bowl; generally constructed of metal with a tray designed to catch ash from the burning charcoal. A tube inside the body of the pipe connects the head with the water bowl. Water bowl: located at the bottom of the waterpipe; generally constructed of glass and partially filled with water. Smoke enters the water through the tube extending from the body of the pipe. Hose: flexible tube attached to the body of the waterpipe just above the water bowl. Waterpipes may have single or multiple hoses. Mouthpiece: connection attached at the end of the hose. Disposable plastic mouthpieces are often used for infection control purposes. After the user inhales through the mouthpiece, a vacuum created in the water bowl causes the smoke to “bubble” through the water and collect in the airspace above the water. The cooled smoke is then transported to the user through the hose and mouthpiece during inhalation. Maassel, the tobacco most often used in waterpipes, contains a mixture of tobacco, dried fruit pulp, honey, and molasses. A variety of flavors are available, including banana, apple, cherry, melon, strawberry, apricot, kiwi, mint, and cappuccino. Other tobacco formulations such as Tumbak and Jurak are less highly sweetened (Maziak et al., 2004). In the U.S., use of waterpipes is becoming increasingly popular among young adults. Hookah bars, lounges, cafes, and restaurants have been emerging in many urban areas of the country including Los Angeles, San Francisco, and New York City. Although many smokers assume the water pipe filters out harmful substances in smoke, there are no data to substantiate this belief. Hookah users inhale tobacco smoke and are at risk for developing dependence and other adverse health-related conditions associated with smoking. Maziak W, Ward KD, Afifi Soweid RA, Eissenberg T. (2004). Tobacco smoking using a waterpipe: A re-emerging strain in a global epidemic. Tob Control 13:327–333. Image courtesy of Mr. Sami Romman /

POTENTIALLY REDUCED-EXPOSURE PRODUCTS (PREPs)
Tobacco formulations altered to minimize exposure to harmful chemicals in tobacco Cigarette-like delivery devices Eclipse, Accord Modified tobacco products Advance, Omni, Quest Oral noncombustible tobacco products Ariva, Revel, Stonewall, Snus No evidence to prove that PREPs reduce the risk of developing tobacco-related disease Potentially reduced-exposure products (PREPs) are tobacco formulations that have been altered to minimize exposure to harmful chemicals in tobacco. PREPs are marketed by the tobacco industry as a safer alternative to conventional cigarettes based on limited studies that show reductions in exposure to nicotine, nitrosamines, polycyclic aromatic hydrocarbons, and carbon monoxide. Most American cigarettes already employ methods of toxin reduction through filtration (use of cellulose acetate filters) or dilution (filter ventilation holes to dilute the smoke). PREPs use different methods to reduce toxin exposure. These methods are described below. Cigarette-like delivery devices (Eclipse, RJ Reynolds; Accord, Philip Morris) These products heat tobacco (without burning it), which reduces the formation of toxins generated during the combustion of tobacco. The Eclipse cigarette looks like a conventional cigarette but contains only a small amount of tobacco. When the user lights the carbon tip on the end of the cigarette, it heats up a column containing glycerin and tobacco, generating a smoke-like vapor that contains nicotine. Similarly, the Accord cigarette is inserted into a specially developed, battery-powered heating device that delivers a specific dose of smoke during each inhalation. Modified tobacco products (Advance, developed by Star Scientific; Omni, Vector Tobacco; Quest, Vector Tobacco) These formulations decrease toxin exposure through the following techniques: Alterations in the tobacco curing process: Star Scientific, Inc., utilizes a proprietary tobacco curing process that reportedly reduces the levels of cancer-causing nitrosamines in tobacco (Advance). Chemically modified tobacco: through the addition of additives such as palladium, Vector Tobacco has created a chemically modified cigarette (Omni) that allegedly reduces the levels of nitrosamines and polycyclic aromatic hydrocarbons. Genetically modified tobacco: Vector tobacco markets a cigarette (Quest) that contains genetically engineered “reduced-nicotine” tobacco. Oral noncombustible tobacco products (Ariva and Stonewall, Star Scientific; Revel, US Smokeless Tobacco; Camel Snus, RJ Reynolds Tobacco) These oral formulations of tobacco are available as small sachets of flavored tobacco (Revel, Snus) or lozenges containing compressed low-nitrosamine tobacco powder (Ariva, Stonewall) that are marketed as cigarette substitutes for situations where smoking is prohibited. Smokeless tobacco products reduce exposure to the harmful products associated with combustion. Although in theory these products reduce the risk of exposure to harmful constituents in tobacco smoke, it is important for clinicians to know that there is no evidence to prove that PREPs reduce the risk of developing tobacco-related disease. Hatsukami D, Hecht S. (2005). Hope or Hazard? What Research Tells Us About “Potentially Reduced-Exposure” Tobacco Products. (Minneapolis: University of Minnesota Transdisciplinary Tobacco Use Research Center). Retrieved May 8, 2006, from Accord image courtesy of Dr. Dorothy Hatsukami - University of Minnesota

FORMS of TOBACCO: SUMMARY
Cigarettes are, by far, the most common form of tobacco used in the U.S. Other forms of tobacco exist and are increasing in popularity. All forms of tobacco are harmful. Attention to all forms of tobacco is needed. To summarize, although cigarettes are by far the most commonly used form of tobacco in the U.S., other forms of tobacco exist. Many of these forms have increased in popularity in recent years, in part because of their social appeal and because of intensive marketing efforts by tobacco companies. However, all forms of tobacco carry significant health risks. As a result, it is important for clinicians to become familiar with the various types of tobacco and to routinely assess their patients’ use of tobacco, not just cigarettes.

NICOTINE PHARMACOLOGY and PRINCIPLES of ADDICTION
This module focuses on the pharmacology of nicotine and principles of addiction.

NICOTINE ADDICTION U.S. Surgeon General’s Report (1988)
Cigarettes and other forms of tobacco are addicting. Nicotine is the drug in tobacco that causes addiction. The pharmacologic and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine. In 1988 the U.S. Surgeon General released a report entitled The Health Consequences of Smoking: Nicotine Addiction. This landmark document summarized the scientific evidence supporting the concept that tobacco products are effective nicotine-delivery systems capable of inducing and sustaining chemical dependence. The major findings of the report were as follows: Cigarettes and other forms of tobacco are addicting. Nicotine is the drug in tobacco that causes addiction. The pharmacologic and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine. The last point is significant in that we, as health care providers, must treat tobacco use and dependence as a serious medical condition. It is a chronic form of brain disease, not just a “bad habit.” Nicotine addiction is a complex disorder that requires treatment directed at both the biological and the behavioral aspects of the disease. U.S. Department of Health and Human Services. (1988). The Health Consequences of Smoking: Nicotine Addiction. A Report of the Surgeon General (DHHS Publication No. PHS ). Washington, DC: U.S. Government Printing Office. Retrieved December 31, 2006, from U.S. Department of Health and Human Services. (1988). The Health Consequences of Smoking: Nicotine Addiction. A Report of the Surgeon General.

CHEMISTRY of NICOTINE N Nicotiana tabacum Natural liquid alkaloid
Pyridine ring Pyrrolidine ring As discussed in the Epidemiology of Tobacco Use module, tobacco and tobacco smoke have numerous constituents. From a pharmacologic perspective, the most important constituent is nicotine. Nicotine, composed of a pyridine ring and a pyrrolidine ring, is one of the few natural alkaloids that exists in the liquid state. Nicotine is a clear, weak base (pKa = 8.0) that turns brown and acquires the characteristic odor of tobacco following exposure to air (Benowitz, 1992; Taylor, 2006). Nicotine mimics the effects of acetylcholine at the acetylcholine receptor site. Benowitz NL. (1992). Cigarette smoking and nicotine addiction. Med Clin N Am 76:415–437. Taylor P. (2006). Agents acting at the neuromuscular junction and autonomic ganglia. In Brunton LL, Lazo JS, Parker KL (eds.), Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw-Hill. Nicotiana tabacum Natural liquid alkaloid Colorless, volatile base pKa = 8.0

PHARMACOLOGY Pharmacokinetics Effects of the body on the drug
Absorption Distribution Metabolism Excretion Effects of the drug on the body Pharmacokinetics Pharmacology is divided into two areas: pharmacokinetics and pharmacodynamics. Pharmacokinetics is defined as the effects that the body has on a drug—specifically, the drug’s absorption, distribution, metabolism, and excretion. Each of these factors significantly influences how a drug affects a given individual. Pharmacodynamics is defined as the effects of a drug on the body. The effects can be either positive (therapeutic effects) or negative (adverse reactions or side effects). The next several slides cover nicotine pharmacokinetics and pharmacodynamics. Then we’ll discuss nicotine addiction as a form of chronic brain disease requiring a multifaceted therapeutic approach. ♪ Note to instructor(s): For a comprehensive review of the metabolism and disposition kinetics of nicotine, refer to Hukkanen, Jacob, & Benowitz (2005). Hukkanen J, Jacob P III, Benowitz NL. (2005). Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57:79–115. Pharmacodynamics

nicotine is readily absorbed.
NICOTINE ABSORPTION Absorption is pH dependent In acidic media Ionized  poorly absorbed across membranes In alkaline media Nonionized  well absorbed across membranes At physiologic pH (7.3–7.5), ~31% of nicotine is unionized To understand nicotine pharmacology, it’s important to know that absorption of nicotine is pH dependent. Because nicotine is a weak base (pKa = 8.0): In acidic media… nicotine is ionized and poorly absorbed across membranes. In alkaline media… nicotine is nonionized and well absorbed across membranes. Under physiologic conditions (pH = 7.3–7.5), approximately 31% of nicotine is nonionized and readily crosses cell membranes (Benowitz, 1992; Hukkanen et al., 2005). Benowitz NL. (1992). Cigarette smoking and nicotine addiction. Med Clin N Am 76:415–437. Hukkanen J, Jacob P III, Benowitz NL. (2005). Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57:79–115. At physiologic pH, nicotine is readily absorbed.

NICOTINE ABSORPTION: BUCCAL (ORAL) MUCOSA
The pH inside the mouth is 7.0. Acidic media (limited absorption) Cigarettes Alkaline media (significant absorption) Pipes, cigars, spit tobacco, oral nicotine products Most American cigarette smoke is acidic. As a result, limited nicotine is absorbed across the buccal (oral) mucosa. In contrast, air-cured tobacco (found in pipe tobacco and cigars) produces smoke with an alkaline pH, which allows for buccal absorption of nicotine. Even pipe or cigar smokers who don’t inhale experience considerable nicotine absorption through the buccal mucosa (Benowitz, 1992). Smokeless tobacco products (snuff and chew) and nicotine gum and lozenge are buffered to an alkaline pH to facilitate absorption of nicotine (Benowitz, 1999). If the pH of the mouth is lowered by drinking acidic beverages (e.g., coffee, juice, or cola), absorption of nicotine from nicotine gum is reduced substantially (Henningfield et al., 1990). This fact is important when counseling patients on the proper use of nicotine gum, lozenge, and oral inhaler. Notably, the tobacco industry documents reveal that the industry alters the ammonia and acid aldehyde chemistry to manipulate the pH of its products, rendering them more addictive. Benowitz NL. (1992). Cigarette smoking and nicotine addiction. Med Clin N Am 76:415–437. Benowitz NL. (1999). Nicotine addiction. Prim Care 26:611–631. Henningfield JE, Radzius A, Cooper TM, Clayton RR. (1990). Drinking coffee and carbonated beverages blocks absorption of nicotine from nicotine polacrilex gum. JAMA 264:1560–1564. Beverages can alter pH, affect absorption.

NICOTINE ABSORPTION: SKIN and GASTROINTESTINAL TRACT
Nicotine is readily absorbed through intact skin. Nicotine is well absorbed in the small intestine but has low bioavailability (30%) due to first- pass hepatic metabolism. Nicotine is readily absorbed across intact skin. This allows for transdermal administration of nicotine as a therapeutic adjunct to tobacco cessation (Taylor, 2006). Conversely, the bioavailability of nicotine in the gastrointestinal tract is limited. Absorption across the gastric mucosa is poor as a result of low gastric pH. In the small intestine, nicotine is well absorbed due to increased pH; however, the systemic bioavailability is low (30%) because it undergoes significant first-pass hepatic metabolism (Benowitz, 1992). Oral nicotine formulations (e.g., sublingual tablets and lozenges) are not subject to first-pass hepatic metabolism. Benowitz NL. (1992). Cigarette smoking and nicotine addiction. Med Clin N Am 76:415–437. Taylor P. (2006). Agents acting at the neuromuscular junction and autonomic ganglia. In Brunton LL, Lazo JS, Parker KL (eds.), Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw-Hill.

NICOTINE ABSORPTION: LUNG
Nicotine is “distilled” from burning tobacco and carried in tar droplets. Nicotine is rapidly absorbed across respiratory epithelium. Nicotine is “distilled” from burning tobacco and carried in droplets to the small airways of the lung. The droplets are composed of water, tar, and alkaloids, including nicotine (Benowitz, 1999). When tobacco smoke reaches the alveoli, nicotine is rapidly absorbed across respiratory epithelial cells due to the following factors (Benowitz, 1999): The pH of the lung is 7.4 (a larger fraction of nicotine is nonionized). The alveolar surface area of the lung is large. The capillary system in the lung is extensive. Benowitz NL. (1999). Nicotine addiction. Prim Care 26:611–631. Lung pH = 7.4 Large alveolar surface area Extensive capillary system in lung

NICOTINE DISTRIBUTION
Nicotine reaches the brain within 11 seconds. Arterial Inhalation of tobacco smoke is an effective means of delivering nicotine to the central nervous system. After inhalation, nicotine is rapidly absorbed across pulmonary epithelium into the arterial circulation, traveling via the carotid arteries to the central nervous system. Nicotine readily penetrates the blood-brain barrier, resulting in transient exposure of the brain to high levels of nicotine. Nicotine has been estimated to reach the brain within 11 seconds of inhalation. Following systemic distribution, brain nicotine levels decline rapidly (Benowitz, 1990). This graph depicts the arterial and venous concentrations of nicotine achieved during cigarette smoking. Within 1 minute after smoking a cigarette, arterial levels of nicotine are nearly seven times the corresponding venous levels (Henningfield et al., 1993). These rapid, high levels of nicotine in the central nervous system produce an almost immediate effect, thereby reinforcing the behavioral act of smoking, which further stimulates repeated administration. Benowitz NL. (1990). Clinical pharmacology of inhaled drugs of abuse: Implications in understanding nicotine dependence. In Chiang CN, Hawks RL (eds.), Research Findings on Smoking of Abused Substances (NIDA Research Monograph 99). Rockville, MD: National Institute on Drug Abuse. Retrieved December 31, 2006, from Henningfield JE, Stapleton JM, Benowitz NL, Grayson RF, London ED. (1993). Higher levels of nicotine in arterial than in venous blood after cigarette smoking. Drug Alcohol Depend 33:23–29. Venous Henningfield et al. (1993). Drug Alcohol Depend 33:23–29.

NICOTINE METABOLISM N H CH3 N 70–80% cotinine ~ 10% other metabolites
10–20% excreted unchanged in urine N CH3 N Nicotine is metabolized extensively in the liver and to a lesser extent in the kidney and lung. Approximately 70–80% of nicotine is metabolized to cotinine, an inactive metabolite (Benowitz et al., 1983), and about 4% is metabolized to nicotine-oxide. The metabolism of nicotine to cotinine is a two-step process likely involving CYP2A6 and aldehyde oxidase. Cotinine is further metabolized to 3′-hydroxycotinine, which undergoes renal elimination. However, nicotine, cotinine, and 3′-hydroxycotinine also undergo glucuronidation. A small fraction (10–20%) of an administered dose of nicotine is excreted as unchanged drug in the urine (Benowitz, 1996; Benowitz & Jacob, 1997; Benowitz et al., 1994). ♪ Note to instructor(s): The daily intake of nicotine can be estimated from a measured plasma cotinine level using the following equation: Daily dose of nicotine (in mg) = plasma cotinine concentration (ng/ml)  0.08 Example: A smoker absorbs, on average, approximately 1 mg of nicotine per cigarette (Benowitz & Jacob, 1984). A person with a plasma cotinine concentration of 300 ng/ml would be expected to smoke approximately 24 cigarettes per day: 300 ng/ml  0.08 = 24 mg = 24 cigarettes (1 mg = 1 cigarette) Benowitz NL. (1996). Pharmacology of nicotine: Addiction and therapeutics. Annu Rev Pharmacol Toxicol 36:597–613. Benowitz NL, Jacob P III. (1984). Daily intake of nicotine during cigarette smoking. Clin Pharmacol Ther 35:499–504. Benowitz NL, Jacob P III. (1994). Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clin Pharmacol Ther 56:483–493. Benowitz NL, Jacob P. (1997). Individual differences in nicotine kinetics and metabolism in humans. In Rapaka RS, Chiang N, Martin BR (eds.), Pharmacokinetics, Metabolism, and Pharmaceutics of Drugs of Abuse (NIDA Research Monograph No. 173; DHHS Publication No ). Rockville, MD: National Institute on Drug Abuse. Benowitz NL, Jacob P, Fong I, Gupta S. (1994). Nicotine metabolic profile in man: Comparison of cigarette smoking and transdermal nicotine. J Pharmacol Exp Ther 268:296–303. Benowitz NL, Kuyt F, Jacob P III, Jones RT, Osman AL. (1983). Cotinine disposition and effects. Clin Pharmacol Ther 34:604–611. 70–80% cotinine ~ 10% other metabolites Metabolized and excreted in urine Adapted and reprinted with permission. Benowitz et al. (1994). J Pharmacol Exp Ther 268:296–303.

NICOTINE EXCRETION Half-life Nicotine t½ = 2 hr Cotinine t½ = 19 hr
Occurs through kidneys (pH dependent; h with acidic pH) Through breast milk The half-life of nicotine in the body is approximately 2 hours. This rapid metabolism of nicotine to inactive compounds underlies tobacco users’ need for frequent, repeated administration of nicotine. With regular tobacco use, significant nicotine levels accumulate during waking hours. The half-life of cotinine (nicotine’s major metabolite) is much longer (18–20 hours). For this reason, cotinine can be used as a more reliable marker of tobacco use and exposure to second-hand smoke. Nicotine and other metabolites are excreted in the urine. Urinary excretion is pH dependent; the excretion rate is increased in acidic urine. Nicotine accumulates in breast milk (Hukkanen et al., 2005) and can be detected in the blood and urine of infants of nursing smokers (Benowitz, 1999; Taylor, 2006). Benowitz NL. (1999). Nicotine addiction. Prim Care 26:611–631. Hukkanen J, Jacob P III, Benowitz NL. (2005). Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57:79–115. Taylor P. (2006). Agents acting at the neuromuscular junction and autonomic ganglia. In Brunton LL, Lazo JS, Parker KL (eds.), Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw-Hill.

NICOTINE PHARMACODYNAMICS
Nicotine binds to receptors in the brain and other sites in the body. Central nervous system Cardiovascular system Exocrine glands Nicotine pharmacodynamics refers to the effects that nicotine has on the body. Nicotine is a potent agent that affects numerous organ systems, including the cardiovascular, endocrine, musculoskeletal, and neurologic systems, as shown in this diagram. Following absorption, nicotine binds to receptors in the brain and other sites in the body, inducing a variety of predominantly stimulant and, to a lesser extent, sedative effects (Taylor, 2006). Taylor P. (2006). Agents acting at the neuromuscular junction and autonomic ganglia. In Brunton LL, Lazo JS, Parker KL (eds.), Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw-Hill. Gastrointestinal system Adrenal medulla Other: Neuromuscular junction Sensory receptors Other organs Peripheral nervous system Nicotine has predominantly stimulant effects.

NICOTINE PHARMACODYNAMICS (cont’d)
Central nervous system Pleasure Arousal, enhanced vigilance Improved task performance Anxiety relief Other Appetite suppression Increased metabolic rate Skeletal muscle relaxation Cardiovascular system  Heart rate  Cardiac output  Blood pressure Coronary vasoconstriction Cutaneous vasoconstriction Pharmacodynamic effects of nicotine on the central nervous system (Benowitz, 1992): Pleasure: Tobacco users commonly report they find tobacco use pleasurable. Arousal, enhanced vigilance: Tobacco use may help with thinking, concentration, and mood elevation. Improved task performance: Nicotine has been shown to increase vigilance and performance for some types of tasks (e.g., repetitive/monotonous tasks). Relief of anxiety: Many tobacco users report reduced anger, tension, and stress after administration. It is not known whether the improvements in mood or task performance are due to relief of nicotine withdrawal symptoms or a direct effect of nicotine on the brain. Pharmacodynamic effects of nicotine on the cardiovascular system: Nicotine’s effects on the cardiovascular system include increased heart rate, cardiac output, and blood pressure as well as cutaneous and coronary vasoconstriction (Benowitz, 1992). After a cigarette is smoked, the smoker’s blood pressure rises by 5–10 mmHg for 15–30 minutes, and the heart rate increases an average of 10–20 beats/min for up to 60 minutes (Benowitz et al., 1988). Studies suggest there is a flat dose-response to the cardiovascular effects of nicotine. This so-called ceiling effect might be due to a rapid but partial development of tolerance to the cardiovascular effects of nicotine (Benowitz, 1997). Other pharmacodynamic effects of nicotine: Nicotine is an effective appetite suppressant and causes modest acute increases in the metabolic rate (Benowitz, 1992). Most people who quit using tobacco will gain weight, although the average person will gain less than 10 pounds (Fiore et al., 2000). Weight gain after tobacco cessation is a major concern for many patients, especially females. Nicotine also causes relaxation of some skeletal muscle (Benowitz, 1992). Benowitz NL. (1992). Cigarette smoking and nicotine addiction. Med Clin N Am 76:415–437. Benowitz NL. (1997). The role of nicotine in smoking-related cardiovascular disease. Prev Med 26:412–417. Benowitz NL, Porchet H, Sheiner L, Jacob P III. (1988). Nicotine absorption and cardiovascular effects with smokeless tobacco use: Comparison with cigarettes and nicotine gum. Clin Pharmacol Ther 44:23–28. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

NEUROCHEMICAL and RELATED EFFECTS of NICOTINE
Dopamine Norepinephrine Acetylcholine Glutamate Serotonin -Endorphin GABA Pleasure, reward Arousal, appetite suppression Arousal, cognitive enhancement Learning, memory enhancement Mood modulation, appetite suppression Reduction of anxiety and tension On a neurochemical level, nicotine induces a variety of central nervous system, cardiovascular, and metabolic effects. Nicotine stimulates the release of many neurotransmitters, which have been associated with the following effects (Benowitz, 1999): Neurotransmitter Effects Dopamine Pleasure, reward Norepinephrine Arousal, appetite suppression Acetylcholine Arousal, cognitive enhancement Glutamate Learning, memory enhancement Serotonin Mood modulation, appetite suppression -Endorphin Reduction of anxiety and tension GABA Reduction of anxiety and tension Nicotine induces a constellation of effects that reinforce tobacco use behavior. Benowitz NL. (1999). The biology of nicotine dependence: From the 1988 Surgeon General’s Report to the present and into the future. Nicotine Tob Res 1(Suppl):S159–S163. Benowitz. (1999). Nicotine Tob Res 1(Suppl):S159–S163.

WHAT IS ADDICTION? ”Compulsive drug use, without medical purpose, in the face of negative consequences” Alan I. Leshner, Ph.D. Former Director, National Institute on Drug Abuse National Institutes of Health Many people believe that addiction is a result of weakness in character and an inability to change one’s behavior. But is it really that simple? Research contradicts this position. Nicotine addiction is a form of chronic brain disease resulting from an alteration in brain chemistry (Leshner, 1997, 1999). Dr. Alan Leshner, the former director of the National Institute on Drug Abuse, simply defines drug addiction as “compulsive use, without medical purpose, in the face of negative consequences” (Leshner, 1997). But how does human behavior fit into this equation? Leshner Al. (1997, April). Drug abuse and addiction are biomedical problems. Hosp Pract (special report):2–4. Leshner AI. (1999). Science-based views of drug addiction and its treatment. JAMA 282:1314–1316.

BIOLOGY of NICOTINE ADDICTION: ROLE of DOPAMINE
stimulates dopamine release is not just a bad habit. Pleasurable feelings Discontinuation leads to withdrawal symptoms. Many smokers believe that smoking/dipping/chewing is simply a bad habit. Research has shown that nicotine addiction is a chronic condition, one with a biological basis. Experts in drug abuse and addiction believe that nicotine addiction is a form of chronic brain disease. Nicotine stimulates the release of brain neurotransmitters, including dopamine, which activates the dopamine reward pathway. This induces feelings of pleasure, which reinforce repeat administration of the drug. With chronic administration, tolerance to the behavioral and cardiovascular effects of nicotine develops over the course of the day. Tobacco users regain sensitivity to the effects of nicotine after overnight abstinence from smoking. When tobacco users abruptly discontinue nicotine they experience symptoms of withdrawal. These withdrawal symptoms serve as a powerful stimulus to repeat nicotine administration (Benowitz, 1992). Benowitz NL. (1992). Cigarette smoking and nicotine addiction. Med Clin N Am 76:415–437. Repeat administration Tolerance develops

DOPAMINE REWARD PATHWAY Ventral tegmental area
Prefrontal cortex Dopamine release Drugs such as cocaine, heroin, amphetamine, and nicotine exert profound effects on the brain. These agents have in common the ability to stimulate the release of the neurotransmitter dopamine in the midbrain. Dopamine induces feelings of euphoria and pleasure and is responsible for activating the dopamine reward pathway (Leshner, 1997). The dopamine reward pathway, as depicted in this simplified diagram, is a network of nervous tissue in the middle of the brain that elicits feelings of pleasure in response to certain stimuli. The important interconnected structures of the reward pathway include the ventral tegmental area (VTA), the nucleus accumbens, and the prefrontal cortex (area of the brain responsible for thinking and judgment). The neurons of the VTA contain the neurotransmitter dopamine, which is released in the nucleus accumbens and in the prefrontal cortex. Behaviors that naturally stimulate the reward pathway include eating to relieve hunger, drinking to alleviate thirst, or engaging in sexual activity. On a primitive, neurochemical level, stimulation of the reward pathway reinforces the behavior so that it will be repeated. Obviously these behaviors are necessary for continued survival of the organism. The reward pathway can also be stimulated by drugs of abuse such as cocaine, opiates, amphetamine, and nicotine. When these unnatural stimuli trigger the reward pathway the same pleasurable feelings are elicited. Researchers believe that, with chronic drug use, the brain becomes chemically altered—transforming a drug user into a drug addict (Leshner, 1997). Consider cigarette smoking as an example. Immediately following inhalation, a bolus of nicotine enters the brain, stimulating the release of dopamine, which induces nearly immediate feelings of pleasure and relief of symptoms of nicotine withdrawal. This rapid dose-response reinforces and perpetuates the smoking behavior. This slide is made available to the public through the National Institute on Drug Abuse Web page, at Adapted with permission by Dr. Rochelle D. Schwartz-Bloom, Duke University. Leshner Al. (1997, April). Drug abuse and addiction are biomedical problems. Hosp Pract (special report):2–4. Stimulation of nicotine receptors Nucleus accumbens Ventral tegmental area Nicotine enters brain

CHRONIC ADMINISTRATION of NICOTINE: EFFECTS on the BRAIN
Nonsmoker Smoker Human smokers have increased nicotine receptors in the prefrontal cortex. High Low Image courtesy of George Washington University / Dr. David C. Perry Chronic administration of nicotine results in an increased number of nicotine receptors in specific regions of the brain (Perry et al., 1999). This upregulation of nicotine receptors leads to the development of tolerance, by which repeated doses of a drug produce less of an effect than did the initial exposure. Perry DC, Davila-Garcia MI, Stockmeier CA, Kellar KJ. (1999). Increased nicotinic receptors in brains from smokers: Membrane binding and autoradiography studies. J Pharmacol Exp Ther 289:1545–1552. Perry et al. (1999). J Pharmacol Exp Ther 289:1545–1552.

NICOTINE PHARMACODYNAMICS: WITHDRAWAL EFFECTS
Depression Insomnia Irritability/frustration/anger Anxiety Difficulty concentrating Restlessness Increased appetite/weight gain Decreased heart rate Cravings* Most symptoms peak 24–48 hr after quitting and subside within 2–4 weeks. ♪ Note to instructor(s): Refer students to the Withdrawal Symptoms Information Sheet handout. This handout describes several symptoms, when they occur postcessation, and how to cope with withdrawal. In addition to being an educational aid for students, it can be copied and distributed to patients who are quitting. When nicotine is discontinued abruptly, the following withdrawal symptoms develop (American Psychiatric Association, 1994; Hughes et al., 1991; Hughes & Hatsukami, 1998): Depression Insomnia Irritability/frustration/anger Anxiety Difficulty concentrating Restlessness Increased appetite/weight gain Decreased heart rate (not measurable through self-report) Cravings* *Cravings is a symptom of tobacco withdrawal that was included in the third edition and revised third edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders; however, this symptom was omitted from the fourth edition (DSM-IV) classifications. Other symptoms of quitting have been described in the literature, and many of these are addressed in the Withdrawal Symptoms Information Sheet. Tobacco users usually experience a strong desire or craving for tobacco. In general, withdrawal symptoms peak 24–48 hours after cessation and gradually dissipate over the next 2–4 weeks. Strong cravings for tobacco may persist for months to years after cessation (Benowitz, 1992; Hughes et al., 1991). American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association. Benowitz NL. (1992). Cigarette smoking and nicotine addiction. Med Clin N Am 76:415–437. Hughes JR, Gust SW, Skoog K, Keenan RM, Fenwick JW. (1991). Symptoms of tobacco withdrawal: A replication and extension. Arch Gen Psychiatry 48:52–59. Hughes JR, Hatsukami D. (1998). Errors in using tobacco withdrawal scale (letter to the editor). Tob Control 7:92–93. HANDOUT American Psychiatric Association. (1994). DSM-IV. Hughes et al. (1991). Arch Gen Psychiatry 48:52–59. Hughes & Hatsukami. (1998). Tob Control 7:92–93. * Not considered a withdrawal symptom by DSM-IV criteria.

NICOTINE ADDICTION CYCLE
To alleviate the symptoms of withdrawal, smokers re-dose themselves throughout the day. This figure depicts the typical nicotine addiction cycle a cigarette smoker experiences on a daily basis. ♪ Note to instructor(s): Orient the students to the following elements on this figure: The jagged line represents venous plasma concentrations of nicotine as a cigarette is smoked every 40 minutes from 8 am to 9 pm. The upper solid line indicates the threshold concentration for nicotine to produce pleasure or arousal. The lower solid line indicates the concentrations at which symptoms of abstinence (i.e., withdrawal symptoms) from nicotine occur. The shaded area represents the zone of nicotine concentrations (neutral zone) in which the smoker is comfortable without experiencing either pleasure/arousal or abstinence symptoms. After smoking the first cigarette of the day, the smoker experiences marked pharmacologic effects, particularly arousal. No other cigarette throughout the day produces the same degree of pleasure/arousal. For this reason, many smokers describe the first cigarette as the most important one of the day. Shortly after the initial cigarette, tolerance begins to develop. Accordingly, the threshold levels for both pleasure/arousal and abstinence rise progressively throughout the day as the smoker becomes tolerant to the effects of nicotine. With continued smoking, nicotine accumulates, leading to an even greater degree of tolerance. As a result, the smoker experiences greater withdrawal symptoms between successive cigarettes. Late in the day, each individual cigarette produces only limited pleasure/arousal; instead, smoking primarily alleviates nicotine withdrawal symptoms. Cessation of smoking overnight allows resensitization of drug responses (i.e., loss of tolerance). Most dependent smokers tend to smoke a certain number of cigarettes per day (usually more than 10) and tend to consume 10–40 mg of nicotine per day to achieve the desired effects of cigarette smoking and minimize the symptoms of nicotine withdrawal (Benowitz, 1992). Benowitz NL. (1992). Cigarette smoking and nicotine addiction. Med Clin N Am 76:415–437. Reprinted with permission. Benowitz. (1992). Med Clin N Am 2:415–437.

NICOTINE ADDICTION Tobacco users maintain a minimum serum nicotine concentration in order to Prevent withdrawal symptoms Maintain pleasure/arousal Modulate mood Users self-titrate nicotine intake by Smoking/dipping more frequently Smoking more intensely Obstructing vents on low-nicotine brand cigarettes As shown in the previous slide, tobacco users tend to carefully titrate, or regulate, their tobacco intake to maintain a relatively constant level of nicotine in the body, in order to Prevent withdrawal symptoms Maintain pleasure/arousal Modulate mood (e.g., to handle stress or anxiety) Although many tobacco users might not think about it consciously, they are able to alter nicotine delivery in a number of ways, including By smoking or dipping more frequently By smoking more intensely (e.g., inhaling deeper or longer, smoking cigarette down to the filter) By obstructing the vents (with fingers or lips) on “light” cigarettes, thereby increasing the amount of nicotine delivered to the lung Benowitz NL. (1999). Nicotine addiction. Prim Care 26:611–631.

ASSESSING NICOTINE DEPENDENCE
Fagerström Test for Nicotine Dependence (FTND) Developed in 1978 (8 items); revised in 1991 (6 items) Most common research measure of nicotine dependence; sometimes used in clinical practice Responses coded such that higher scores indicate higher levels of dependence Scores range from 0 to 10; score of greater than 5 indicates substantial dependence In research, and sometimes in clinical practice, it is useful to be able to measure a patient’s level of nicotine dependence. The most commonly used scale for assessing nicotine dependence is the Fagerström Test for Nicotine Dependence (FTND). The FTND, which originally was an 8-item scale called the Fagerström Tolerance Questionnaire, consists of the following 6 items (Heatherton et al., 1991): How soon after you wake up do you smoke your first cigarette? Within 5 minutes, 6–30 minutes, 31–60 minutes, after 60 minutes Do you find it difficult to refrain from smoking in places where it is forbidden? Yes, No Which cigarette would you hate most to give up? The first one in the morning, Any other How many cigarettes per day do you smoke? 10 or less, 11–20, 21–30, 31 or more Do you smoke more frequently during the first hours after waking than during the rest of the day? Do you smoke if you are so ill that you are in bed most of the day? ♪ Note to instructor(s): Refer students to the FTND handout, which lists the items, describes the scoring, and presents cutoffs for categories of dependence. The scale is perhaps the most commonly used research measure of nicotine dependence, but it also can be used in clinical practice. As shown on the scoring sheet, the responses are coded such that higher scores indicate higher levels of nicotine dependence. The total scores, after summing the items, range from 0 to 10. Although there are no established cutoffs for score interpretations, many researchers and clinicians generally consider scores of greater than 5 indicative of substantial dependence. Modified versions of the scale have been developed and tested for use with spit tobacco users (Severson & Hatsukami, 1999) and adolescents (Prokhorov et al., 1998). Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO. (1991). The Fagerström Test for Nicotine Dependence: A revision of the Fagerström Tolerance Questionnaire. British Journal of Addiction 86:1119–1127. Prokhorov AV, Koehly LM, Pallonen UE, Hudmon KS. (1998). Adolescent nicotine dependence measured by the modified Fagerström Tolerance Questionnaire at two time points. J Child Adol Subst Use 7:35–47. Severson HH, Hatsukami DK. (1999). Smokeless tobacco cessation. Prim Care 26:529–551. HANDOUT Heatherton et al. (1991). British Journal of Addiction 86:1119–1127.

CLOSE TO HOME © 2000 John McPherson.
Patients often describe tobacco cessation as the most difficult achievement of their life. Tobacco users can be very creative in the methods they choose for quitting, as is illustrated in this cartoon. CLOSE TO HOME © 2000 John McPherson. Reprinted with permission of UNIVERSAL PRESS SYNDICATE. All rights reserved.

FACTORS CONTRIBUTING to TOBACCO USE
Environment Tobacco advertising Conditioned stimuli Social interactions Physiology Genetic predisposition Coexisting medical conditions Tobacco Use Nicotine is a powerful drug capable of inducing a variety of pharmacologic effects, including an alteration in brain chemistry. However, tobacco addiction is more than just a brain disease. It is a complex process involving the interplay of many factors (pharmacologic, environmental, and physiologic) that influence an individual’s decision to use tobacco (Benowitz, 1992). As such, treatment of addiction requires a multifaceted approach (Lerman et al., 2005; Leshner, 1999). This slide depicts important factors that influence tobacco use behavior. Environmental factors: Tobacco industry advertising: For years, the tobacco industry has engineered major marketing plans to design more addictive cigarettes and to defy the public regarding the hazards of smoking. Their multibillion-dollar marketing effort is an important contributor to tobacco use. Conditioned stimuli: All drug-taking behavior is learned, a result of conditioning. Drug-taking behavior is reinforced by the consequences of the pharmacologic actions of the drug. At the same time, smokers begin to associate specific moods, situations, or environmental factors with nicotine’s reward effects. The association between such cues and anticipated drug effects and the resulting urge to smoke is another type of conditioning. For example, people often smoke cigarettes in specific situations, such as after a meal or with coffee or alcoholic beverages. The association between smoking and these other events, repeated many times, causes the environmental situations to become powerful cues for the urge to smoke. A nondrug example of this type of conditioning is the desire to eat popcorn at the movies or hot dogs at baseball games. Other aspects of smoking (e.g., manipulation of smoking materials, taste, smell, feel of smoke in the throat) become associated with the pleasurable effects of smoking. Even unpleasant moods can become conditioned cues for smoking. For example, a smoker may learn that not having a cigarette provokes irritability, a common nicotine withdrawal symptom. Smoking a cigarette relieves withdrawal symptoms. After repeated similar experiences, a smoker may come to regard irritability from any source, such as stress or frustration, as a cue for smoking. Conditioning is a major factor that causes relapse. As such, it must be addressed as a component of behavioral therapy for nicotine addiction. Social interactions: Having family or peer-group members who smoke increases the likelihood of tobacco use and, therefore, addiction. Among adolescents, peer pressure is often a reason for initiating tobacco use. Pharmacologic factors: As discussed previously, there is a pharmacologic basis for a nicotine-dependent individual’s decision to use tobacco. Physiologic factors: Experts now believe that some individuals have a genetic predisposition for nicotine addiction. Additionally, the impact of coexisting medical conditions (especially psychiatric conditions) increases an individual’s likelihood of using and becoming dependent on tobacco. Benowitz NL. (1992). Cigarette smoking and nicotine addiction. Med Clin N Am 76:415–437. Lerman C, Patterson F, Berrettini W. (2005). Treating tobacco dependence: State of the science and new directions. J Clin Oncol 23:311–323. Leshner AI. (1999). Science-based views of drug addiction and its treatment. JAMA 282:1314–1316. Pharmacology Alleviation of withdrawal symptoms Weight control Pleasure

TOBACCO DEPENDENCE: A 2-PART PROBLEM
Physiological Behavioral Treatment The addiction to nicotine Medications for cessation The habit of using tobacco Behavior change program Tobacco dependence is a chronic brain disease and is a condition that requires a two-prong approach for maximal treatment effectiveness. Prolonged tobacco use of tobacco results in tobacco dependence, which is characterized as a physiological dependence (addiction to nicotine) and behavioral habit of using tobacco. Addiction can be treated with FDA-approved medications for smoking cessation, and the behavioral habit can be treated through behavior change programs, such as individualized counseling and group or online cessation programs. The Clinical Practice Guideline for treating tobacco use and dependence (Fiore et al., 2000), which summarizes more than 6,000 published articles, advocates the combination of behavioral counseling with pharmacotherapy in treating patients who smoke. ♪ Note to instructor(s): Specific methods for treating tobacco use and dependence are covered in detail in the Assisting Patients with Quitting and Aids for Cessation modules. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Treatment should address the physiological and the behavioral aspects of dependence.

NICOTINE PHARMACOLOGY and ADDICTION: SUMMARY
Tobacco products are effective delivery systems for the drug nicotine. Nicotine is a highly addictive drug that induces a constellation of pharmacologic effects. Nicotine activates the dopamine reward pathway in the brain, which reinforces continued tobacco use. Tobacco users who are dependent on nicotine self-regulate tobacco intake to maintain pleasurable effects and prevent withdrawal. To summarize: Tobacco products are effective delivery systems for the drug nicotine. Nicotine is a highly addictive drug that induces a constellation of pharmacologic effects. Nicotine activates the dopamine reward pathway in the brain, which reinforces continued tobacco use. Tobacco users who are dependent on nicotine self-regulate their tobacco intake to maintain pleasurable effects and prevent withdrawal.

NICOTINE PHARMACOLOGY and ADDICTION: SUMMARY (cont’d)
Nicotine dependence is a form of chronic brain disease. Tobacco use is a complex disorder involving the interplay of the following: Pharmacology of nicotine (pharmacokinetics and pharmacodynamics) Environmental factors Physiologic factors Treatment of tobacco use and dependence requires a multifaceted treatment approach. Nicotine dependence is a form of chronic brain disease. Tobacco use is a complex disorder involving the interplay of the following: Nicotine pharmacology, including pharmacokinetics and pharmacodynamics Environmental factors Physiologic factors Treatment of tobacco use and dependence requires a multifaceted approach. This topic is covered in the remainder of the program.

DRUG INTERACTIONS with SMOKING
Many interactions between tobacco smoking and medications have been identified (Kroon 2006; Schein, 1995; Zevin & Benowitz, 1999). As discussed previously, tobacco smoke is a complex mixture of gaseous and particulate matter. It is widely recognized that the polycyclic aromatic hydrocarbons (PAHs) are largely responsible for the majority of drug interactions with smoking. PAHs, which are the products of incomplete combustion of tobacco, are found in appreciably large quantities in tobacco smoke and are potent inducers of hepatic microsomal (cytochrome P450) enzymes. Although other substances in tobacco smoke, including acetone, pyridines, benzene, nicotine, carbon monoxide, and heavy metals (e.g., cadmium), may also interact with hepatic enzymes, their effects appear to be less significant. ♪ Note to instructor(s): It is important to emphasize that the drug interactions described in this module refer to interactions between medications and constituents in tobacco smoke, and NOT between medications and nicotine. ♪ Note to instructor(s): This module reviews the clinically significant drug interactions reported with tobacco smoking and nicotine. Other interactions are described in the Drug Interactions with Smoking handout. The references noted below provide overviews of drug interactions with smoking. Kroon LA. (2006). Drug interactions and smoking: raising awareness for acute and critical care providers. Crit Care Nurs Clin North Am 18:53–62. Schein JR. (1995). Cigarette smoking and clinically significant drug interactions. Ann Pharmacother 29:1139–1148. Zevin S, Benowitz NL. (1999). Drug interactions with tobacco smoking. Clin Pharmacokinet 36:425–438.

PHARMACOKINETIC DRUG INTERACTIONS with SMOKING
Drugs that may have a decreased effect due to induction of CYP1A2: Caffeine Fluvoxamine Olanzapine Tacrine Theophylline Absorption of inhaled insulin is 2- to 5-fold higher in smokers than in nonsmokers Use is contraindicated in current smokers and patients who quit less < 6 months prior to treatment Tobacco smoke may interact with medications through pharmacokinetic or pharmacodynamic mechanisms. Pharmacokinetic interactions affect the absorption, distribution, metabolism, or elimination of other drugs, potentially causing an altered response. Polycyclic aromatic hydrocarbons (PAHs) in tobacco are responsible for induction of cytochrome P450 enzymes (CYP1A1, CYP1A2, and possibly CYP2E1). The majority of drug interactions with tobacco smoke are pharmacokinetic, resulting from the induction of drug-metabolizing enzymes (especially CPY1A2) by compounds in tobacco smoke. All of these drugs are metabolized via CYP1A2. Induction of CYP1A2 by PAHs in tobacco smoke will increase metabolism, resulting in potentially clinically significant decreased pharmacologic effects of the following drugs: Caffeine: Clearance is increased by 56%. It is reasonable to advise patients to decrease their intake of caffeinated beverages when quitting smoking, because nicotine withdrawal effects might be enhanced by increased caffeine levels. Fluvoxamine (Luvox): Clearance of this antidepressant is increased by 24%; plasma concentrations are decreased by 32%. Yoshimura et al. (2002) determined that plasma fluvoxamine concentrations were significantly lower in smokers (by 39%) compared with nonsmokers. Dosage modifications are not routinely recommended, but smokers might require higher dosages. Olanzapine (Zyprexa): Clearance of this atypical antipsychotic is increased by 40–98%. Gex-Fabry et al. (2003) showed that smokers had significantly lower concentrations (by 12%) compared with nonsmokers. Dosage modifications are not routinely recommended, but smokers might require higher dosages to achieve clinical response (Carrillo et al. 2003). Tacrine (Cognex): Clearance is substantially increased in smokers. The manufacturer states that mean plasma tacrine concentrations in smokers are threefold lower than those achieved in nonsmokers. The half-life of tacrine is decreased by 50%. Smokers might require higher dosages. Theophylline: Clearance is increased by 58–100%; half-life is decreased by 63%. Closely monitor theophylline levels if smoking is initiated, discontinued, or changed. Maintenance doses are considerably higher in smokers. Within 7 days of smoking cessation, theophylline clearance might decrease by 35%. Note: A similar interaction occurs with aminophylline. A key pharmacokinetic interaction involves the absorption of inhaled insulin, which is increased 2- to 5-fold in smokers when compared to non-smokers (Pfizer, 2006). Because clinical studies suggest patients who smoke and receive inhaled insulin are at an increased risk for hypoglycemia, use of inhaled insulin is contraindicated in patients who are current smokers and in recent quitters who have been abstinent for less than six months prior to treatment (Pfizer, 2006). Following smoking cessation, a patient titrated on any of the above medications may experience enhanced pharmacologic effects or toxicity. Carrillo JA, Herraiz AG, Ramos SI, Gervasini G, Vizcaino S, Benitez J. (2003). Role of the smoking-induced cytochrome P450 (CYP)1A2 and polymorphic CYP2D6 in steady-state concentration of olanzapine. J Clin Psychopharmacol 23:119–127. Gex-Fabry M, Balant-Gorgia AE, Balant LP. (2003). Therapeutic drug monitoring of olanzapine: The combined effect of age, gender, smoking and comedication. Ther Drug Monit 25:46–53. Pfizer, Inc. (2006, May). Exubera Package Insert. New York, NY. Yoshimura R, Ueda N, Nakamura J, Eto S, Matsushita M. (2002). Interaction between fluvoxamine and cotinine or caffeine. Neuropsychobiology 45:32–35. Smoking cessation will reverse these effects. HANDOUT

PHARMACODYNAMIC DRUG INTERACTIONS with SMOKING
Smokers who use combined hormonal contraceptives have an increased risk of serious cardiovascular adverse effects: Stroke Myocardial infarction Thromboembolism This interaction does not decrease the efficacy of hormonal contraceptives. Pharmacodynamic interactions alter the expected response or actions of other drugs. In general, these are less common than pharmacokinetic interactions, but the potential interaction of combined oral contraceptives (those containing both estrogen and progestin) with smoking is important. The use of combined hormonal contraceptives (e.g., oral, patch, ring) should be strongly discouraged in women who are regular smokers. The cardiovascular effects of combined hormonal contraceptives include venous thromboembolism (deep leg vein thrombosis and pulmonary embolism) and myocardial infarction and ischemic or hemorrhagic stroke (arterial events). Considerable epidemiologic evidence indicates that cigarette smoking substantially increases the risk of adverse cardiovascular events (mainly stroke and myocardial infarction [MI]) in women using oral contraceptive (OC) agents (Burkman et al., 2004; Seibert et al., 2003). This risk also applies to other delivery forms (e.g., patch, ring). This risk is age-related: The overall risk of death from cardiovascular disease in low-dose OC users who smoke is 3.3 per 100,000 women aged 15–34 years versus 29.4 per 100,000 women aged 35–44 years. The corresponding risk of death from cardiovascular disease in nonsmoking women who use OC is lower: 0.65 per 100,000 women aged 15–34 years and 6.21 per 100,000 women aged 35–44 years (Schwingl et al., 1999). A case-control study of 627 women younger than age 45 with a nonfatal first MI and 2,947 control subjects assessed whether use of low-dose OC increased the risk of MI. The odds ratio for current OC use was 2.5 among heavy smokers (25 cigarettes/day) and 1.3 among nonsmokers and light smokers. Current OC use together with heavy smoking increased the risk of MI ~30 times that of nonsmokers who did not use OC (Rosenberg et al., 2001). Accordingly, experts generally recommend that oral contraceptive use is contraindicated in women who are 35 years of age or older AND heavy (at least 15 cigarettes/day) smokers (Schiff et al., 1999; World Health Organization, 2004). Smoking is not a contraindication for use of emergency contraception. A 1988 study indicated that approximately one-fourth of oral contraceptive users were smokers; half of these women were heavy smokers (Barrett et al., 1994). This suggests there are ample opportunities for health care providers to intervene with women who use tobacco. At the very minimum, women should be advised to consult with their physician about alternative birth control methods. However it is far preferable for women to quit smoking. It is important to note, however, that this interaction does not decrease the efficacy of hormonal contraceptives. Barrett DH, Anda RF, Escobedo LG. (1994). Trends in oral contraceptive use and cigarette smoking. Arch Fam Med 3:438–443. Burkman R, Schlesselman JJ, Zieman M. (2004). Safety concerns and health benefits associated with oral contraception. Am J Obstet Gynecol 190:S5–S22. Grimes DA, Raymond EG. (2002). Emergency contraception. Ann Intern Med 137: Rosenberg L, Palmer JR, Rao S, Shapiro S. (2001). Low-dose oral contraceptive use and the risk of myocardial infarction. Arch Intern Med 161:1065–70. Schiff I, Bell WR, Davis V, Kessler CM, Meyers C, Nakajima S, Sexton BJ. (1999). Oral contraceptives and smoking, current considerations: Recommendations of a consensus panel. Am J Obstet Gynecol 180:S383–S384. Schwingl PJ, Ory HW, Visness CM. (1999). Estimates of the risk of cardiovascular death attributable to low-dose oral contraceptives in the United States. Am J Obstet Gynecol 180:241–249. Seibert C, Barbouche E, Fagan J, Myint E, Wetterneck T, Wittemyer M. (2003). Prescribing oral contraceptives for women older than 35 years of age. Ann Intern Med 138:54–64. World Heath Organization. (2004). Low dose combined oral contraceptives. In Medical Eligibility Criteria for Contraceptive Use, 3rd ed. Geneva, Switzerland: World Health Organization, pp. 1–26. Retrieved May 8, 2006, from Women who are 35 years of age or older AND smoke at least 15 cigarettes per day are at significantly elevated risk.

DRUG INTERACTIONS with SMOKING: SUMMARY
Clinicians should be aware of their patients’ smoking status: Clinically significant interactions result not from nicotine but from the combustion products of tobacco smoke. These tobacco smoke constituents (e.g., polycyclic aromatic hydrocarbons; PAHs) may enhance the metabolism of other drugs, resulting in a reduced pharmacologic response. Smoking might adversely affect the clinical response to the treatment of a wide variety of conditions. To summarize: Clinicians should be aware of their patients’ smoking status for the following reasons: Smoking has the potential for pharmacokinetic and pharmacodynamic interactions. Clinically significant interactions result not from nicotine but from the combustion products of tobacco smoke. Constituents in tobacco smoke (e.g., polycyclic aromatic hydrocarbons; PAHs) may enhance the metabolism of other drugs, resulting in a reduced pharmacologic response. Smoking might adversely affect the clinical response to the treatment of a wide variety of conditions.

ASSISTING PATIENTS with QUITTING
This module focuses on behavioral techniques for helping patients to quit using tobacco. Tobacco use is a complex, addictive behavior. As a result, helping a patient to quit requires a behavioral intervention, not simply a drug. Research shows that adding pharmacotherapy to a behavioral intervention substantially increases patients’ likelihood of quitting (Fiore et al., 2000). Clinicians are educators who routinely interact with patients to discuss health-related issues. With the introduction of pharmaceutical products to aid cessation, clinicians’ potential role for helping patients to quit using tobacco has expanded. It is our job, as educators, to ensure that students in the health professions are equipped for this role. ♪ Note to instructor(s): Rx for Change also provides a parallel (optional) module that applies the Transtheoretical Model of Change as a framework for assisting patients with quitting. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

CLINICAL PRACTICE GUIDELINE for TREATING TOBACCO USE and DEPENDENCE
Released June 2000 Sponsored by the Agency for Healthcare Research and Quality of the U.S. Public Heath Service with Centers for Disease Control and Prevention National Cancer Institute National Institute for Drug Addiction National Heart, Lung, & Blood Institute Robert Wood Johnson Foundation In June 2000, the U.S. Public Health Service published a Clinical Practice Guideline for treating tobacco use and dependence (Fiore et al., 2000). This guideline, which summarizes more than 6,000 articles from the literature, reaches a consensus on strategies and recommendations designed to assist health care providers in delivering state-of-the-art interventions for smoking cessation. The slides that follow describe feasible, practical, and effective behavioral strategies that clinicians can apply when assisting patients with quitting. These strategies derive from recommendations set forth in the Clinical Practice Guideline. The complete guideline, along with supportive materials, is available at Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

EFFECTS of CLINICIAN INTERVENTIONS
Fiore et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS. 1.0 1.1 (0.9,1.3) 1.7 (1.3,2.1) 2.2 (1.5,3.2) n = 29 studies Compared to smokers who receive no assistance from a clinician, smokers who receive such assistance are 1.7–2.2 times as likely to quit successfully for 5 or more months. Decades of research tell us that clinicians can have an important impact on their patients’ likelihood of achieving cessation. A meta-analysis of 29 studies determined that patients who received a tobacco cessation intervention from a nonphysician clinician or a physician clinician were 1.7 and 2.2 times as likely to quit (at 5 or more months postcessation), respectively, compared with patients who did not receive such an intervention (Fiore et al., 2000). Self-help materials were only slightly better than no clinician. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

The CLINICIAN’s ROLE in PROMOTING CESSATION
Tobacco users expect to be encouraged to quit by health professionals. Screening for tobacco use and providing tobacco cessation counseling are positively associated with patient satisfaction (Barzilai et al., 2001). Tobacco users expect to be encouraged to quit by health professionals. In a study examining whether health habit counseling affects patient satisfaction, Barzilai et al. (2001) determined that of 12 health habits examined (exercise, diet, alcohol history, alcohol counseling, tobacco history, tobacco counseling, passive tobacco exposure, contraception and condom use, substance use history, substance use counseling, STD prevention, and counseling about HIV testing or prevention), only tobacco history and tobacco counseling were significantly associated with full satisfaction with the clinician visit. A clinician who does not address tobacco use tacitly implies that quitting is not important. Barzilai DA, Goodwin MA, Zyzanski SJ, Stange KC. (2001). Does health habit counseling affect patient satisfaction? Prev Med 33:595–599. Failure to address tobacco use tacitly implies that quitting is not important. Barzilai et al. (2001). Prev Med 33:595–599.

The 5 A’s ASK ADVISE ASSESS ASSIST ARRANGE
The Clinical Practice Guideline (Fiore et al., 2000) delineates five key components for tobacco cessation interventions. These components, referred to as the 5 A’s, offer a practical method for implementing tobacco counseling in clinical practice. The 5 A’s are as follows: Ask Advise Assess Assist Arrange ♪ Note to instructor(s): The 5 A’s presented in the guideline are a modified form of the National Cancer Institute’s original 5 A’s (Anticipate [tobacco use], Ask, Advise, Assist, and Arrange; Frankowski & Secker-Walker, 1994; Glynn & Manley, 1990). ♪ Note to instructor(s): Throughout this module, ask students to refer to their Tobacco Cessation Counseling Guidesheet (ancillary handout). The slides in this module are designed to parallel the guidesheet. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Frankowski BL, Secker-Walker RH. (1994). Pediatricians’ Role in Smoking Prevention and Cessation (Smoking and Tobacco Control Monograph No. 5; NIH Publication No ). Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute. Glynn TJ, Manley MW. (1990). How to Help Your Patients Stop Smoking: A National Cancer Institute Manual for Physicians (NIH Publication No ). Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute. ASSESS ASSIST ARRANGE HANDOUT Fiore et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS.

The 5 A’s (cont’d) ASK Ask about tobacco use
“Do you ever smoke or use any type of tobacco?” “I take time to ask all of my patients about tobacco use—because it’s important.” “Medication X often is used for conditions linked with or caused by smoking. Do you, or does someone in your household smoke?” “Condition X often is caused or worsened by smoking. Do you, or does someone in your household smoke?” ASK Ask. Tobacco smoke has the potential to interact with many medications, altering both drug levels and efficacy. Tobacco use also can induce early onset of disease and exacerbate existing medical conditions. It is appropriate, if not essential, for clinicians to assess and document each patient’s tobacco use status, preferably at each visit. Asking about tobacco use should be considered to be as important as evaluating vital signs during a routine medical screening, and when obtaining a medication history, clinicians should ask about tobacco in the same way that they would ask about any other drug. Clinicians also should consider including a query about tobacco use on the new patient profile form. At a minimum, the form should assess tobacco use status (i.e., current, former, never). Appropriate language for assessing tobacco use status would be: “Do you ever smoke or use any type of tobacco?” This question will capture not only cigarette smoking but all forms of tobacco use. The query also can be linked to the clinician’s knowledge of a patient’s disease status or medication profile. For example: “Medication X often is used for conditions linked with or caused by smoking. Do you, or does someone in your household smoke?” or “Condition X often is caused or worsened by smoking. Do you, or does someone in your household smoke?” When clinicians ask about tobacco use, it is important that they take a genuine and sensitive approach, conveying concern for their patients’ well-being. A judgmental tone likely will not result in accurate disclosure of tobacco use.

The 5 A’s (cont’d) ADVISE
tobacco users to quit (clear, strong, personalized, sensitive) “It’s important that you quit as soon as possible, and I can help you.” “I realize that quitting is difficult. It is the most important thing you can do to protect your health now and in the future. I have training to help my patients quit, and when you are ready, I will work with you to design a specialized treatment plan.” ADVISE Advise. It is the clinician’s responsibility to assist patients in improving their health. Patients who use tobacco should be strongly advised to quit. At the very least, these patients should be advised to consider quitting. The message should be clear and strong, yet personalized and sensitive. The message must be delivered without judgment—or the clinician will likely waste that “teachable moment” and potentially alienate his or her patient. Tone and manner should convey a concern for the patient’s well-being as well as a commitment to help him or her quit—when the patient is ready. Consider the following statements: “It’s important that you quit as soon as possible, and I can help you.” “I realize that quitting is difficult. It is the most important thing you can do to protect your health now and in the future. I have training to help my patients quit, and when you are ready, I will work with you to design a specialized treatment plan.” The clinician can personalize the message by tying tobacco use to current health or illness; its social and economic costs; the patient’s motivation level and readiness to quit; or the impact of tobacco use on children, others in the household and in their environment, and pets. For example: “If you continue to smoke, your [disease] will worsen/fail to improve.” Using a genuine and sensitive approach that acknowledges the difficulty of what is being requested, the clinician might move the patient forward in the process of preparing to quit.

The 5 A’s (cont’d) ASSESS Assess readiness to make a quit attempt
Assist with the quit attempt Not ready to quit: provide motivation (the 5 R’s) Ready to quit: design a treatment plan Recently quit: relapse prevention ASSIST Assess. After the clinician advises the patient to quit, the next step is to assess the patient’s readiness, or willingness, to try to quit. Is the patient considering quitting in the next month? Or did he or she quit recently? Assist. The patient’s readiness to try to quit will define the next course of action, which is delivering an intervention tailored to his or her needs. By being a good listener and gathering appropriate information, the clinician can tailor the interventions effectively. A patient who is not ready to quit will receive a very different type of intervention than will one who is ready to quit in the upcoming weeks. For the patient who is not ready to quit, a motivational intervention should be provided, by applying the 5 R’s (to be discussed later). If the patient is ready to quit (i.e., in the next 30 days), a treatment plan should be designed, including counseling and pharmacotherapy (except when contraindicated). The clinician could suggest that the patient enroll in a structured, intensive tobacco cessation program, to increase the likelihood of quitting— this is particularly important for persons who are at high risk of relapse or for patients who are highly dependent, refractory smokers (i.e., having made multiple serious quit attempts). Other patient populations that might be particularly well suited for structured programs include adolescent smokers, pregnant smokers, and patients with coexisting psychiatric conditions. A patient who recently quit (i.e., in the past 6 months) will need continued support and encouragement, and reminders regarding the need to abstain from all tobacco use—even a puff. A patient who has been off of tobacco for more than 6 months typically is relatively stable but often needs to be reminded to remain vigilant for potential triggers for relapse.

PROVIDE ASSISTANCE THROUGHOUT THE QUIT ATTEMPT
The 5 A’s (cont’d) Arrange follow-up care ARRANGE Number of sessions Estimated quit rate* 0 to 1 12.4% 2 to 3 16.3% 4 to 8 20.9% More than 8 24.7% Arrange. The clinician should make certain to arrange for follow-up care and patient monitoring. With each contact, it is important to document the counseling session. These records can provide a starting point for subsequent discussions. Follow-up visits can be arranged in several ways. For example, the clinician can do the following: “Check in” with the patient when he or she next returns. Schedule specific follow-up visits to discuss tobacco cessation. Invite the patient to enroll in a tobacco cessation group with which the clinician is affiliated. With prior approval, call the patient at home to see how he or she is progressing. (If a message is left, the clinician should not indicate that he or she is calling regarding a quit attempt—this might be private information that the patient does not want others to hear.) Document key dates (e.g., quit dates, tobacco-free anniversaries); acknowledge important milestones. A follow-up contact should be scheduled within the first week after the quit date. The next follow-up is recommended within the first month. Further follow-up contact should be scheduled as needed or indicated. During the follow-up contacts, the patient should be congratulated for success. If tobacco use has occurred, the circumstances should be reviewed and a commitment sought to return to total abstinence. The patient should be reminded that lapses (slips) occur as part of the normal learning process and should be viewed as such. Pharmacotherapy use should be assessed, including compliance and side effects experienced. When appropriate, referral to more intensive treatment should be considered. According to the Clinical Practice Guideline (Fiore et al., 2000), multiple patient contacts are associated with higher quit rates. The estimated quit rates, based on number of treatment sessions (i.e., counseling contact sessions) are presented in this slide. Even brief interventions (i.e., asking about tobacco use and advising to quit) can increase patients’ readiness to quit. In a meta-analysis of 17 trials assessing the effects of cessation advice from medical practitioners (Lancaster & Stead, 2004), brief advice was associated with an increased likelihood of quitting (odds ratio, 1.74) versus no advice (or usual care), which is equivalent to an absolute change in cessation rate of 2.5%; in addition, more intensive advice led to a higher likelihood of quitting when compared to more minimal advice (odds ratio, 1.44). ♪ Note to instructor(s): A dose-response relationship also exists for the counseling session length and the total amount of contact time (combining across treatment sessions). The greater the amount of time spent with the patient, the more likely the patient is to achieve abstinence (Fiore et al ). Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Lancaster T, Stead L. (2004). Physician advice for smoking cessation. Cochrane Database Syst Rev (4):CD * 5 months (or more) postcessation PROVIDE ASSISTANCE THROUGHOUT THE QUIT ATTEMPT Fiore et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS.

READINESS to make a quit attempt
The 5 A’s: REVIEW ASK about tobacco USE ADVISE tobacco users to QUIT As a final review, the 5 A’s are as follows: Ask about tobacco use. Advise tobacco users to quit. Assess readiness to make a quit attempt. Assist with the quit attempt. Arrange follow-up care. Each of these is a key component of comprehensive tobacco cessation counseling interventions. ASSESS READINESS to make a quit attempt ASSIST with the QUIT ATTEMPT ARRANGE FOLLOW-UP care

The (DIFFICULT) DECISION to QUIT
Faced with change, most people are not ready to act. Change is a process, not a single step. Typically, it takes multiple attempts. Historically, clinicians have been trained to provide action-oriented, “just do it” counseling interventions. It’s important to recognize that not all patients have the same level of commitment, or readiness, to take action. When faced with change, most people (about 70%) are not ready to act (Prochaska et al., 1992). Patients at different stages of readiness to quit require different kinds of interventions. Counseling should be tailored to patients’ readiness to quit (often referred to as their “stage of change”). This is particularly important when counseling through various steps of tobacco cessation. Consider the following: Some patients are determined smokers…they might never quit! Some might know that they need to quit but have tried and failed so many times that they have no confidence in their ability to quit. Some are considering quitting but might not have gathered the courage or information necessary to make a serious quit attempt. Some will be ready to set a quit date. Others might have stopped recently but remain highly vulnerable to relapse. And some will have been smoke-free for at least 6 months yet remain at risk for relapse. In most cases, behavior change is a process, not a single step. The process ranges from not thinking about making a change to successful implementation of a behavioral change over a sustained period of time. Typically, it takes multiple attempts before success is achieved. Prochaska JO, DiClemente CC, Norcross JC. (1992). In search of how people change: Applications to addictive behaviors. Am Psychol 47:1102–1114. HOW CAN I LIVE WITHOUT TOBACCO?

HELPING SMOKERS QUIT IS a CLINICIAN’S RESPONSIBILITY
TOBACCO USERS DON’T PLAN TO FAIL. MOST FAIL TO PLAN. Clinicians have a professional obligation to address tobacco use and can have an important role in helping patients plan for their quit attempts. Tobacco users don’t plan to fail in their quit attempts. But most fail to plan. Health care providers have a professional obligation to help patients improve their health. This includes addressing tobacco use and helping patients to quit. Clinicians serve as facilitators in the process, calling attention to the need to quit, advising patients to quit, assisting with the quit attempt, and monitoring patient progress over time. For current smokers, the goal is to move tobacco users forward in their decision to quit. However, the decision to quit ultimately lies in the hands of the patient. THE DECISION TO QUIT LIES IN THE HANDS OF EACH PATIENT.

ASSESSING READINESS to QUIT
Patients differ in their readiness to quit. STAGE 1: Not ready to quit in the next month STAGE 2: Ready to quit in the next month Prior to providing assistance with tobacco cessation, it is helpful to assess each patient’s readiness to quit (Fiore et al., 2000). Patients can be categorized into four discrete categories: Stage 1: Not ready to quit in the next month Stage 2: Ready to quit in the next month Stage 3: Recent quitter, quit with the past 6 months Stage 4: Former tobacco user, quit more than 6 months ago Assessing a patient’s readiness to quit enables clinicians to deliver relevant, appropriate counseling messages. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. STAGE 3: Recent quitter, quit within past 6 months STAGE 4: Former tobacco user, quit > 6 months ago Assessing a patient’s readiness to quit enables clinicians to deliver relevant, appropriate counseling messages.

ASSESSING READINESS to QUIT (cont’d)
For most patients, quitting is a cyclical process, and their readiness to quit (or stay quit) will change over time. Not thinking about it Former tobacco user Not ready to quit This diagram emphasizes that behavior change is a process. Over time, patients often cycle into and out of the different stages. They might quit for a while, then return to tobacco use before they quit again for good. This movement between the stages is normal and is to be expected, particularly for an addictive behavior that patients know they need to stop but might not have the time, energy, or will to stop at the present time. For this reason, it is important to determine the patient’s readiness to commit to quitting at each contact. Do not assume that patients who inquire about quitting are ready to quit. Commonly, they are just thinking about it and gathering information. Similarly, do not assume that a patient who asks for a prescription for bupropion or nicotine replacement therapy or who presents at a pharmacy to purchase these medications is ready to quit. Learning about the different stages of readiness to quit will help clinicians gain a better understanding of why it is important to think of behavior change as a process, not an event. For most people, the process of quitting is characterized by a series of quit attempts and subsequent relapses—on average, former smokers report 10.8 quit attempts over a period of 18.6 years before quitting for good (Hazelden Foundation, 1998). Hazelden Foundation. (1998). Survey on current and former smokers—1998. Center City, MN: Hazelden Foundation. Retrieved December 31, 2006, from Relapse Thinking about it, not ready Recent quitter Assess readiness to quit (or to stay quit) at each patient contact. Ready to quit

IS a PATIENT READY to QUIT?
Does the patient now use tobacco? Is the patient now ready to quit? Provide treatment The 5 A’s Promote motivation Yes No Did the patient once use tobacco? Prevent relapse* Encourage continued abstinence Yes No *Relapse prevention interventions not necessary if patient has not used tobacco for many years and is not at risk for re-initiation. This flow chart, which is presented in the Clinical Practice Guideline for treating tobacco use and dependence (Fiore et al., 2000), describes how to determine a patient’s readiness to quit and the general types of interventions that should be applied. Treatment for patients who are ready to quit should include all five of the key counseling components (the 5 A’s). Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Fiore et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS.

STAGE 1: Not ready to quit Not thinking about quitting in the next month Some patients are aware of the need to quit. Patients struggle with ambivalence about change. Patients are not ready to change, yet. Pros of continued tobacco use outweigh the cons. Most patients who use tobacco will not be ready to quit in the immediate future. These patients generally fall into one of two categories: Those who are not aware of any need to change—the problem is not yet on their radar screen. Those who are unwilling or unable to change—commonly because they are defensive about their negative health behavior or because they are too discouraged to change (perhaps because of prior failed attempts). Health care providers commonly label patients in this stage as difficult or unmotivated. Many of these patients simply are not ready. They struggle with ambivalence and see the pros (positive effects) of tobacco use as being more important than the cons (negative effects). The goal of interventions at this stage is to encourage patients to start thinking about quitting. Prochaska JO, Goldstein MG. (1991). Process of smoking cessation. Clin Chest Med 12:727–735. GOAL: Start thinking about quitting.

STAGE 1: NOT READY to QUIT Counseling Strategies
DOs Strongly advise to quit Provide information Ask noninvasive questions; identify reasons for tobacco use “Envelope” Raise awareness of health consequences/concerns Demonstrate empathy, foster communication Leave decision up to patient DON’Ts Persuade “Cheerlead” Tell patient how bad tobacco is, in a judgmental manner Provide a treatment plan Patients at this stage might be defensive or resistant to interventions that would require them to take action right away. When counseling a patient who is not ready to quit, it is important to demonstrate understanding and empathy, to foster ongoing communication, and to ask questions noninvasively. Instead of pressuring the patient for an immediate behavioral shift, gently raise the patient’s awareness of the health consequences of continued tobacco use. Messages that either emphasize the cons of tobacco use or deemphasize the pros of tobacco use help move the patient forward in the process of change. It is useful to tailor messages based on the patient’s health history, such as highlighting how tobacco use can induce early onset of particular diseases for which the patient may be at risk, or how it can exacerbate existing conditions. An approach that might be effective with parents is discussing how smoking can negatively affect their children’s health and increase the likelihood that their children will grow up to be smokers. Strongly encourage patients to quit, yet emphasize that the decision to quit, or not to quit, is theirs. To gauge a patient’s level of resistance to quitting, ask him or her, “If I were to give you an envelope, what would the message inside need to say for you to consider quitting?” If the patient says, “There is nothing that you could write that would make me consider quitting,” then there is little that you can do at this point, except to (1) stress the importance of quitting for the patient’s health, (2) suggest that the patient not rule out the possibility of quitting, and (3) offer to assist the patient with quitting, should the patient change his or her mind. Also, asking patients what brand they smoke and whether they buy tobacco in large quantities can provide insight regarding a patient’s likelihood of being ready to quit. Aggressive efforts to persuade the patient into making a change are not advisable during this stage. Likewise, high-spirited “cheerleading” may only heighten the patient’s resistance at this stage. Also, be careful not to use a judgmental approach in telling patients that tobacco is bad for them. It is not yet time to provide a treatment plan, although it might be useful to inform patients of the various options available. Offer assistance. Make it clear that it is an ongoing, standing offer, which the patient can accept whenever he or she is ready.

STAGE 1: NOT READY to QUIT Counseling Strategies (cont’d)
The 5 R’s—Methods for increasing motivation: Relevance Risks Rewards Roadblocks Repetition Tailored, motivational messages For patients who are not ready to quit, clinicians can deliver tailored, motivational messages by applying the 5 R’s: Relevance: Encourage the patient to indicate why quitting is personally relevant. Be as specific as possible. Motivational information has the most impact if it is relevant to the patient’s disease status or risk, family or social situation (e.g., having children in the home), health concerns, age, sex, and other important patient characteristics (e.g., prior quitting experience, personal barriers to cessation). Risks: Ask the patient to identify consequences of tobacco use. Suggest and highlight those that seem most relevant to the patient and emphasize that other forms of tobacco (such as smokeless, or lower-tar-level cigarettes) will not eliminate the risks. Risks of tobacco use are discussed in the Epidemiology of Tobacco Use and Pathophysiology of Tobacco-Related Disease modules. Rewards: Ask the patient to identify benefits of quitting. Highlight those that seem relevant to the patient. Examples of benefits of cessation are discussed in the Epidemiology of Tobacco Use module. Roadblocks: Ask the patient to identify barriers to quitting and potential methods for circumventing each barrier. Suggest and highlight those that seem most relevant to the patient. Common barriers include withdrawal symptoms, fear of failure, weight gain, lack of support, depression, and enjoyment of tobacco. Repetition: Repeat the motivational intervention whenever possible. Tobacco users who have failed in previous quit attempts should be reminded that most people make repeated quit attempts before they are successful. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Fiore et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS.

STAGE 1: NOT READY to QUIT A Demonstration
CASE SCENARIO: MS. STEWART ♪ Note to instructor(s): After presenting this slide (read the case scenario to the audience), enact Case Scenario A by either (1) showing Video #1 or (2) having students role-play this case scenario in front of the class. If you choose option (2), it is best to select students in advance, and provide them with the instructor guidelines for this case. Have one student play the patient and one student play the clinician. Appropriate dialogue is provided in the instructor guidelines. The two slides that follow can be used as “case debriefing” aids. Case B also is provided for instructors who would like to enact two different scenarios. ♪ Note to instructor(s): Video #1 is a pharmacy-based counseling session, but similar strategies should be used, regardless of clinician type or setting. You are a clinician providing care to Ms. Stewart, a 55-year-old patient with emphysema. She uses two different inhalers to treat her emphysema. VIDEO #1

STAGE 1: NOT READY to QUIT Case Scenario Synopsis
Ask about tobacco use Link inquiry to knowledge of disease Assess readiness to quit Aware of need to quit; not ready yet Advise to quit Discuss implications for disease progression “I will help you, when you are ready” Note the following key points about this scenario: The clinician used knowledge of the patient’s disease state to initiate the conversation about tobacco use. The clinician assessed the patient’s interest in quitting and explored the patient’s beliefs about her ability to quit, as well as some of the perceived benefits of and barriers to quitting. The clinician expressed concern about the patient’s health, informed the patient that her smoking will worsen her condition, and advised the patient to quit. The clinician offered to assist the patient, should she decide to quit.

STAGE 1: NOT READY to QUIT Case Scenario Synopsis (cont’d)
The clinician has Established a relationship Established herself as a resource Planted a seed to move patient forward Opened a door to facilitate further counseling The clinician has provided an appropriate intervention for a patient who is not ready to quit. The goal was to try to plant a seed to get the patient thinking about quitting, to move the patient forward in the process of change. And, in doing so, the clinician has fostered communication and a relationship with one of his or her patients. Note that this brief, motivational intervention required very little time (approximately 2 minutes).

GOAL: Achieve cessation.
ASSESSING READINESS to QUIT (cont’d) STAGE 2: Ready to quit Ready to quit in the next month Patients are aware of the need to, and the benefits of, making the behavioral change. Patients are getting ready to take action. At the second stage in the continuum of change, patients are ready to quit in the very near future (likely in the next month). These patients recognize the need to change and the benefits to be had by quitting. They are getting ready to quit. Often, they might have made a quit attempt in the past year. The goal is to assist these patients in achieving cessation. GOAL: Achieve cessation.

STAGE 2: READY to QUIT Three Key Elements of Counseling
Assess tobacco use history Discuss key issues Facilitate quitting process Three key elements of tobacco cessation counseling: Assess tobacco use history Discuss key issues Facilitate the quitting process Assessing tobacco use history and discussing key issues are important information-gathering steps of counseling. Clinicians must develop an understanding of their patients’ unique history and perspective on tobacco use before facilitating the quitting process. ♪ Note to instructor(s): These three elements parallel those presented on the Tobacco Cessation Counseling Guidesheet (ancillary handout).

STAGE 2: READY to QUIT Assess Tobacco Use History
Praise the patient’s readiness Assess tobacco use history Current use: type(s) of tobacco, brand, amount Past use: duration, recent changes Past quit attempts: Number, date, length Methods used, compliance, duration Reasons for relapse This stage represents a window of opportunity for helping a patient make a quit attempt. Clinicians should do the following prior to making treatment recommendations: Praise the patient’s readiness to quit. Assess tobacco use history, including current use, past use, and history of quit attempts: Current use of tobacco: What types of tobacco are used? What brand? How much? Past use of tobacco: How long has the patient been using tobacco? Has the patient changed his or her level of tobacco use recently? Past quit attempts: How many quit attempts has the patient made, how long was he or she off of tobacco, and when was the last quit attempt? What methods were used? What worked? What didn’t work? If medications were used, how were they used? What factors contributed to relapse (e.g., medication noncompliance, situational factors)? Identifying reasons for relapse can provide important information for an upcoming quit attempt.

STAGE 2: READY to QUIT Discuss Key Issues
Reasons/motivation to quit (or avoid relapse) Confidence in ability to quit (or avoid relapse) Triggers for tobacco use What situations lead to temptations to use tobacco? What led to relapse in the past? Routines/situations associated with tobacco use Key issues to address include the following: Discuss reasons and motivations for wanting to quit. Ask the patient to think about why it is important, to him or her, to adopt a tobacco-free lifestyle. What are the patient’s motivations for wanting to quit? Discuss whether the patient has concerns about the effects of second-hand smoke on others. How confident is the patient in his or her ability to quit? Ideally, the patient will be highly confident, but many will lack confidence because of previously failed attempts. By providing additional support and working with the patient in designing the treatment plan, a clinician can infuse confidence into the patient. It will be “different,” this time, because the patient will be more prepared. Discuss specific triggers for tobacco use. Triggers might include negative affect, being around other smokers, meal times, alcohol or coffee consumption, cravings for tobacco, time pressures, or other situations such as celebrating with others. Triggers should be identified prior to quitting, while the patient is still smoking “normally.” Encourage patients to think about the times and places where they smoke or use tobacco, each time they do so. This provides important insight into a person’s tobacco use behavior, including the circumstances that underlie the need or desire for tobacco. Having a clear understanding of the behavior will help a person to be more effective when attempting to change it. Determine whether there are certain routines or situations that the patient associates with tobacco use (e.g., when drinking coffee, while driving in the car, while bored or stressed, after meals, after sex). Does the patient use tobacco in response to stress? What types of triggers or situations invoke stress-related tobacco use? Assess whether the patient has a social network of friends, family, and coworkers that is supportive of the quit attempt. Encourage the patient to enlist the support of others; invite significant other to attend cessation counseling sessions. Encourage the patient’s housemates who are tobacco users to quit simultaneously. Assess whether the patient is concerned about postcessation weight gain. Advise the patient to quit first, then work on weight maintenance a month or more later. However, if concern about weight gain is a barrier to quitting, then it should be addressed simultaneously with the quit attempt. Discuss any concerns that the patient might have about withdrawal symptoms. When drinking coffee While driving in the car When bored or stressed While watching television While at a bar with friends After meals During breaks at work While on the telephone While with specific friends or family members who use tobacco

STAGE 2: READY to QUIT Discuss Key Issues (cont’d)
Stress-Related Tobacco Use THE MYTHS THE FACTS “Smoking gets rid of all my stress.” “I can’t relax without a cigarette.” There will always be stress in one’s life. There are many ways to relax without a cigarette. Stress is often cited as the primary reason for smoking. This slide presents the myths versus the facts. Smokers often confuse the relief of their nicotine withdrawal with the feeling of relaxation. The goal is to help patients to realize that tobacco is the problem, not the solution. Smokers confuse the relief of withdrawal with the feeling of relaxation. STRESS MANAGEMENT SUGGESTIONS: Deep breathing, shifting focus, taking a break.

Social Support for Quitting ADVISE PATIENTS TO DO THE FOLLOWING: Ask family, friends, and coworkers for support, for example, not to smoke around them and not to leave cigarettes out Talk with their health care provider Get individual, group, or telephone counseling The Clinical Practice Guideline (Fiore et al., 2000) cites both intra- and extra-treatment social support as key ingredients for quitting. Advise patients to do the following: Ask family, friends, and coworkers for support, for example, not to smoke around them and not to leave cigarettes out. Talk with their health care provider. Get individual, group, or telephone counseling support. Programs often are provided at local hospitals and health centers. Tobacco cessation counseling is available, to all Americans, by calling QUIT-NOW. Patients who receive social support and encouragement enhance their odds of quitting successfully. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Patients who receive social support and encouragement are more successful in quitting.

Most smokers gain fewer than 10 pounds, but there is a wide range.
HERMAN ® is reprinted with permission from LaughingStock Licensing Inc., Ottawa, Canada All rights reserved. Most smokers gain fewer than 10 pounds, but there is a wide range. Postcessation weight gain is an important consequence of tobacco cessation that often is also a barrier to quitting. The majority of tobacco users gain weight after quitting. Studies suggest that most quitters will gain less than 10 pounds, but a broad range of weight gains have been reported, with up to 10% of quitters gaining as much as 30 pounds (Fiore et al., 2000). In a study of nearly 6,000 smokers who were followed for 5 years after quitting, the mean weight gain during the follow-up period was 19.2 pounds and 16.7 pounds among women and men, respectively (O’Hara et al., 1998). The weight- suppressing effects of tobacco are well known. However, the mechanisms to explain why most successful quitters gain weight are not completely understood. Smokers have been found to have an approximately 10% higher metabolic rate compared with nonsmokers (Perkins, 1992). Higher caloric intakes have been documented after cessation (Hatsukami et al., 1993), and it has been speculated that the increased caloric intake might be caused either by an increase in appetite or by quitters eating more because the taste buds have become more receptive after cessation and foods taste better (Hamilton et al., 1992). Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Hamilton E, Whitney E, Sizer F. (1992). Nutrition:Concepts and Controversies, 6th ed. St. Paul: West Publishing. Hatsukami D, LaBounty L, Hughes J, Laine D. (1993). Effects of tobacco abstinence on food intake among cigarette smokers. Health Psychol 12:499–502. O'Hara P, Connett JE, Lee WW, Nides M, Murray R, Wise R. (1998). Early and late weight gain following smoking cessation in the Lung Health Study. Am J Epidemiol 148:821–830. Perkins KA. (1992). Metabolic effects of cigarette smoking. J Appl Physiol 72:401–409.

Concerns about Weight Gain Discourage strict dieting while quitting Recommend physical activity Encourage healthful diet, planning of meals, and inclusion of fruits Suggest increasing water intake or chewing sugarless gum Recommend selection of nonfood rewards Maintain patient on pharmacotherapy shown to delay weight gain Refer patient to specialist or program Many patients will be concerned about weight gain after quitting; these patients should be discouraged from strict dieting while quitting (Fiore et al., 2000). To reduce weight gain, patients can engage in regular physical activity and adhere to a healthful diet (as opposed to strict dieting). Patients should carefully plan and prepare meals to avoid binge eating, increase fruit and water intake to create a feeling of fullness, and chew sugarless gum or eat sugarless candies. Advise patients to select nonfood rewards. Consider maintaining these patients on pharmacotherapy that has been shown to delay weight gain, such as nicotine gum or bupropion. Patients also can be referred to a dietary specialist or weight maintenance program. ♪ Note to instructor(s): Research studies have shown that patients who attempt to modify their diet at the same time as quitting smoking are less likely to succeed in smoking cessation than are patients who just try to quit smoking. We recommend that clinicians advise most of their patients to quit smoking first, then work on issues of weight gain. The average gain of less than 10 pounds is less detrimental to one’s health than is smoking, but it is not prudent for clinicians to overlook patients’ concerns about weight gain. If concern about weight gain is a key barrier to quitting, it should be addressed simultaneously with quitting. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

Concerns about Withdrawal Symptoms Most pass within 2–4 weeks after quitting Cravings can last longer, up to several months or years Often can be ameliorated with cognitive or behavioral coping strategies Refer to Withdrawal Symptoms Information Sheet Symptom, cause, duration, relief Most symptoms peak 24–48 hours after quitting and subside within 2–4 weeks. As described in the Pharmacology of Nicotine and Principles of Addiction module, cessation is associated with a wide range of withdrawal symptoms. Specific symptoms included in the 4th edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; APA, 1994) are depression, insomnia, irritability/frustration/anger, anxiety, difficulty concentrating, restlessness, increased appetite/weight gain, and decreased heart rate. Cravings is a symptom of tobacco withdrawal that was included in the third edition and revised third edition of the DSM; however, this symptom was omitted from the DSM-IV classifications. Other symptoms of quitting have been described in the literature, and many of these are addressed in the Withdrawal Symptoms Information Sheet . When counseling a quitter, it is important to address concerns about withdrawal symptoms. The extent of withdrawal symptoms that a smoker experiences when abstinent from tobacco will be a function of his or her level of dependence. In general, the physiologic symptoms of withdrawal pass within 2–4 weeks after quitting (Hughes et al., 1991). However, some former tobacco users experience cravings for months or even years after quitting. These cravings typically are psychologically motivated, not physiologic, and can be ameliorated using cognitive or behavioral coping strategies. Sometimes a simple change of surroundings can help alleviate cravings, such as leaving the office to step outside for a breath of fresh air, or taking a quick walk up a flight or two of stairs to get some exercise. ♪ Note to instructor(s): At this time, direct students to pull out their one-page Withdrawal Symptoms Information Sheet. This handout describes each symptom, when it occurs after cessation, and potential coping methods. The Withdrawal Symptoms Information Sheet can be used as a resource for distribution to patients. American Psychiatric Association (APA). (1994). Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC: APA. Hughes JR, Gust SW, Skoog K, Keenan RM, Fenwick JW. (1991). Symptoms of tobacco withdrawal: A replication and extension. Arch Gen Psychiatry 48:52–59. HANDOUT

STAGE 2: READY to QUIT Facilitate Quitting Process
Discuss methods for quitting Discuss pros and cons of available methods Pharmacotherapy: a treatment, not a crutch! Importance of behavioral counseling Set a quit date Recommend Tobacco Use Log Helps patients to understand when and why they use tobacco Identifies activities or situations that trigger tobacco use Can be used to develop coping strategies to overcome the temptation to use tobacco In facilitating the quitting process, clinicians should Discuss the pros and cons of different methods for quitting. It is important to elicit the patient’s point of view—each patient will have his or her own perceptions of the different methods. Encourage use of pharmacotherapy in addition to behavioral counseling. Many patients will feel that pharmacotherapy is a “crutch”—these patients should be advised that tobacco use is a chronic condition that alters brain chemistry and that, when feasible and not contraindicated, pharmacotherapy should be used because it increases the chances of quitting. It should be viewed as a treatment, not a crutch. Help the patient set a quit date. The quit date should be at least 3 days but not longer than 2 weeks from the current date. Recommend the Tobacco Use Log, if appropriate. This tool helps patients to identify moods, activities, or situations that trigger the desire to smoke or use other forms of tobacco. Triggers for tobacco use might include negative affect, being around other smokers, meal times, alcohol or coffee consumption, cravings for tobacco, stress, time pressures, or other situations such as celebrating with others. Triggers should be identified prior to quitting, while the patient is still smoking “normally.” Information gathered in the log can be used to develop coping strategies to overcome the temptation to use tobacco. ♪ Note to instructor(s): Have students refer to the Tobacco Use Log handout. The Tobacco Use Log is most appropriate for patients who are ready to quit, but it can be used with any patient who wants to learn more about his or her tobacco use behavior. This exercise provides important insight into the circumstances that underlie the need or desire for tobacco. Having a clear understanding of the behavior will help a person to be more effective when attempting to change it. Tobacco Use Log adapted from The Wrap Sheet and the Daily Cigarette Count (Wrap Sheet). In: The Washington State Pharmacists Association. (1997). “Smoking Cessation Training: Pharmacists Becoming Smoking Cessation Counselors,” pp. 3, 25. HANDOUT

STAGE 2: READY to QUIT Facilitate Quitting Process (cont’d)
Tobacco Use Log: Instructions for use Continue regular tobacco use for 3 or more days Each time any form of tobacco is used, log the following information: Time of day Activity or situation during use “Importance” rating (scale of 1–3) Instructions for use: The Tobacco Use Log is a documentation tool that is kept with the patient’s tobacco. For example, the Tobacco Use Log could be folded and wrapped around the cigarette pack or can of snuff with a rubber band. The log should be readily available at the times when the patient uses the tobacco. Through careful documentation of tobacco use over a period of several days, patient-specific tobacco usage patterns become evident. Instruct the patient to continue his or her regular tobacco use for a period of at least 3 days (including one non–work day). It is preferable to complete the Tobacco Use Log for 7 consecutive days, because usage patterns may fluctuate as a function of the day of the week (e.g., weekends vs. work days). The patient should not attempt to reduce tobacco use during this time. The intent is to document current tobacco use habits and patterns. The following information should be noted in the Tobacco Use Log each time any form of tobacco is used: Time of day Brief description of the activity or situation while using the tobacco; other persons present at that time. Encourage the patient to think about the times and places where he or she uses tobacco, each time it is used. It is important for the patient to understand these cues so that effective coping strategies can be developed to overcome the temptation to use tobacco. Rating of the patient’s perceived importance of using the tobacco, at that time, using the following scale: 1 = Very important (would have missed it a great deal) 2 = Moderately important 3 = Not very important (would not have missed it) Log sheets should be reviewed prior to the quit attempt, to identify situations that trigger tobacco use and to develop coping strategies to prevent relapse. Cognitive and behavioral coping strategies are described in the slides that follow. Review log to identify situational triggers for tobacco use; develop patient-specific coping strategies

Discuss coping strategies Cognitive coping strategies Focus on retraining the way a patient thinks Behavioral coping strategies Involve specific actions to reduce risk for relapse HANDOUT The clinician and patient should discuss and develop effective cognitive and behavioral coping strategies for handling specific situations in which a person will be tempted to use tobacco. Research shows that using both cognitive and behavioral strategies increases a patient’s likelihood of quitting (Prochaska & DiClemente, 1992). These strategies are described in the next few slides. ♪ Note to instructor(s): Have students refer to the Coping with Quitting: Cognitive and Behavioral Strategies handout. This handout provides specific examples of coping strategies for various situations. Prochaska JO, DiClemente CC. (1992). Stages of change in the modification of problem behaviors. In: Progress in Behavior Modification, edited by Hersen M, Eisler RM, Miller PM. Sycamore, IL: Sycamore, pp. 184–218.

Cognitive Coping Strategies Review commitment to quit Distractive thinking Positive self-talk Relaxation through imagery Mental rehearsal and visualization Cognitive strategies focus on retraining the way a patient thinks. Many quitters panic because they are thinking about tobacco after they quit, and this leads to relapse. Thinking about cigarettes (or other forms of tobacco) is normal. The trick is not to dwell on the thought. As tobacco users move toward sustained abstinence, they learn to recognize that thinking about a cigarette doesn’t mean they need to have one. Some examples of cognitive strategies include the following: Review of one’s commitment to quitting can help, including reminding oneself that cravings and temptations are temporary and will pass. Sometimes it helps a patient to announce, either silently or out loud, “I want to be a nonsmoker, and the temptation will pass.” Or each morning, to look in the mirror and say, “I am proud that I made it through another day without tobacco!” Deliberate, distractive thinking can help the patient move current thought processes to issues other than craving or temptation to use tobacco. Positive self-talks, or “pep-talks,” involve saying things such as, “I can do this,” or reminding oneself of previous difficult situations in which tobacco use was avoided successfully. Relaxation through imagery helps the patient to center the mind on positive, relaxing thoughts. This can help to ease the anxiety, stress, and negative moods that may trigger tobacco use. Mental rehearsal and visualization involves envisioning situations that might arise and how best to handle them. This method is commonly used by athletes prior to a game. For example, a goalie might envision (or enact, during pregame warmups) how to block different types of shots or plays from opposing players. In the case of smoking, a person might envision what would happen if he or she were offered a cigarette by a friend—he or she would mentally craft and rehearse a response and perhaps even practice it by saying it out loud.

Cognitive Coping Strategies: Examples Thinking about cigarettes doesn’t mean you have to smoke one: “Just because you think about something doesn’t mean you have to do it!” Tell yourself, “It’s just a thought,” or “I am in control.” Say the word “STOP!” out loud, or visualize a stop sign. When you have a craving, remind yourself: “The urge for tobacco will only go away if I don’t use it.” As soon as you get up in the morning, look in the mirror and say to yourself: “I am proud that I made it through another day without tobacco.” This slide presents several examples of cognitive statements that can be used while quitting.

Behavioral Coping Strategies Control your environment Tobacco-free home and workplace Remove cues to tobacco use; actively avoid trigger situations Modify behaviors that you associate with tobacco: when, what, where, how, with whom Substitutes for smoking Water, sugar-free chewing gum or hard candies (oral substitutes) Take a walk, diaphragmatic breathing, self-massage Actively work to reduce stress, obtain social support, and alleviate withdrawal symptoms Behavioral strategies involved specific actions for coping with the effects of quitting and reducing risk for relapse. The effectiveness of these strategies may be patient specific, meaning that one technique will work better for some patients than for others. To determine which strategies work best for a specific patient, a clinician must understand the patient’s reasons for tobacco use and routines or situations with which tobacco use is associated. General approaches include enhanced control of the environment. Tobacco-free environments (e.g., home and workplace) can increase chances of success (e.g., Bauer et al., 2005; Chapman et al., 1999; Fichtenberg & Glantz, 2002). Patients should be advised to remove cues for tobacco use, modify behaviors associated with tobacco use, and actively avoid specific situations in which tobacco use is likely to occur. Oral substitutes for tobacco use include drinking water; chewing sugar-free gum; or sucking on hard, sugar-free candies. Taking walks helps to change the tobacco user’s environment and also increases circulation and oxygenation while burning calories. Deep breathing can have a relaxing effect, and research suggests that self-massage might reduce cravings (Hernandez-Reif et al., 1999). Social support is considered a key component of successful treatment plans (Fiore et al., 2000). Patients should be encouraged to call upon members of their support network as needed. Withdrawal symptoms are inevitable, especially with patients who are heavy users of tobacco products. It is important that clinicians educate their patients so that they know what to expect, how to alleviate specific symptoms, and how long to expect the symptoms to last. ♪ Note to instructor(s): Specific behavioral strategies for common cues or causes of relapse (stress, alcohol, other tobacco users, oral gratification needs, automatic smoking routines, postcessation weight gain, cravings for tobacco) are presented in the Coping with Quitting: Cognitive and Behavioral Strategies handout. Bauer JE, Hyland A, Li Q, Steger C, Cummings KM. (2005). A longitudinal assessment of the impact of smoke-free worksite policies on tobacco use. Am J Public Health 95:1024–1029. Chapman S, Borland R, Scollo M, Bronson RC, Dominello A, Woodward S. (1999). The impact of smoke-free workplaces on declining cigarette consumption in Australia and the United States. Am J Public Health 89:1018–1023 . Fichtenberg CM, Glantz SA. (2002). Effect of smoke-free workplaces on smoking behavior: systematic review. BMJ 325:188–191. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Hernandez-Reif M, Field T, Hart S. (1999). Smoking cravings are reduced by self-massage. Prev Med 28:28–32.

Provide medication counseling Promote compliance Discuss proper use, with demonstration Discuss concept of “slip” versus relapse “Let a slip slide.” Offer to assist throughout quit attempt Follow-up contact #1: first week after quitting Follow-up contact #2: in the first month Additional follow-up contacts as needed Congratulate the patient! It is imperative that clinicians counsel patients on their pharmacotherapy regimens (proper use, with demonstration as needed) and encourage patients to maintain close compliance with the prescribed regimen. Many cessation medications are designed to alleviate withdrawal; patients should be advised to take the medications as prescribed, not as needed. If a patient waits until he or she is in dire need of nicotine, it is too late. Nicotine replacement therapies do not have the same rapid onset of action as tobacco formulations. Prior to embarking on a quit attempt, the patient should be strongly advised not to smoke an occasional cigarette, or to have “just one drag” off of a friend’s cigarette. These are precursors for a full relapse. But, the patient should know the difference between a slip and a full relapse. A slip is a situation in which a person smokes one or just a few cigarettes. Although this can lead to a full relapse, it is not a complete failure, and it should be considered part of the learning process. If this occurs, encourage the patient to think through the scenario and determine the trigger(s) for smoking. Suggest coping strategies that will enable the patient to avoid smoking in similar situations. The last of the 5 A’s is to arrange follow-up. At this point, the clinician should summarize treatment plans and offer to assist throughout the quit attempt. Follow-up contact is recommended within the first week after quitting and a few weeks later (within the first month), with additional follow-up contacts as needed until the patient is stable in his or her new role as a nonuser of tobacco (Fiore et al., 2000). At follow-up contact, it is important to reassess the patient’s commitment to quitting and his or her confidence in quitting. The patient’s response will, in part, be a reflection of his or her confidence in the treatment plan. As needed, offer resources and referrals (e.g., to other health care providers, telephone cessation hotlines). Finally, congratulate the patient for making the important decision to quit. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

GOAL: Remain tobacco-free for at least 6 months.
ASSESSING READINESS to QUIT (cont’d) STAGE 3: Recent quitter Actively trying to quit for good Patients have quit using tobacco sometime in the past 6 months and are taking steps to increase their success. Withdrawal symptoms occur. Patients are at risk for relapse. Patients who quit (in the past 6 months) are considered recent quitters. These patients are taking steps to enhance the likelihood that they can successfully quit by using medications such as nicotine replacement therapy. They dispose of unused cigarettes and remove lighters and other smoking apparatus from their homes and cars. They alter their routines to avoid habituated smoking patterns. These patients likely are experiencing withdrawal symptoms—some pleasant (such as revived taste buds) and some not so pleasant (such as cravings, irritability, and weight gain). Recent quitters are at high risk for relapse. The goal is to help them remain tobacco-free. GOAL: Remain tobacco-free for at least 6 months.

STAGE 3: RECENT QUITTERS Evaluate the Quit Attempt
Status of attempt Ask about social support Identify ongoing temptations and triggers for relapse (negative affect, smokers, eating, alcohol, cravings, stress) Encourage healthy behaviors to replace tobacco use Slips and relapse Has the patient used tobacco at all—even a puff? Medication compliance, plans for termination Is the regimen being followed? Are withdrawal symptoms being alleviated? How and when should pharmacotherapy be terminated? Recent quitters face many challenges in adopting their new behavior (not smoking). During the quit attempt, clinicians should carefully tailor interventions to match each patient’s needs. It is an opportunity to problem solve, or intervene, most creatively. Here are the basic strategies for evaluating a patient’s quit attempt: Inquire about available social support. Identify temptations and triggers relapse. Key triggers are negative affect, being around other tobacco users, eating, drinking alcohol, cravings for tobacco, and stress. Suggest coping strategies as needed, to remove or modify cues in the environment that make a person want to use tobacco, such as removing ashtrays, not entering an office where smokers are congregating, and not drinking alcohol if it will increase the likelihood of tobacco use. Encourage healthful behaviors to replace smoking (e.g., drinking water, exercise). Determine whether the patient has had any slips or has relapsed. Evaluate the treatment regimen. Is compliance with medications adequate? Are withdrawal symptoms being alleviated? How and when should pharmacotherapy be terminated?

STAGE 3: RECENT QUITTERS Facilitate Quitting Process
Relapse Prevention Congratulate success! Encourage continued abstinence Discuss benefits of quitting, problems encountered, successes achieved, and potential barriers to continued abstinence Ask about strong or prolonged withdrawal symptoms (change dose, combine or extend use of medications) Promote smoke-free environments Social support Discuss ongoing sources of support Schedule additional follow-up as needed; refer to support groups Relapse prevention is an important component of tobacco cessation interventions and should be part of every encounter with patients who recently quit using tobacco. At a minimum, the quitter should be congratulated for his or her successes and should be strongly encouraged to remain tobacco-free. Relapse prevention interventions should include a discussion of the patient’s perceived benefits of quitting, challenges during the process, successes achieved (specific situations in which the patient was tempted to use tobacco but resisted), and potential barriers to continued abstinence (e.g., depression, alcohol use, weight gain, stress, and other tobacco users who are not supportive of cessation). For patients who are feeling a sense of loss after quitting (some individuals feel as though they have lost a best friend), acknowledge their feelings and reassure them that the feelings will subside over time. Identify and recommend other activities that the particular patient views as rewarding. For patients who are complying with their pharmacotherapy regimens but continue to have strong or prolonged withdrawal symptoms, consider adding, combining, or extending use of medications. For a recent quitter, it is important to attempt to reduce relapse risk by promoting tobacco-free environments (e.g., in the home and workplace). Assess the patient’s level of ongoing support for the quit attempt. Schedule follow-up visits or calls, as needed to prevent relapse. If necessary, refer the patient to a tobacco cessation support group in the community.

STAGE 4: Former tobacco user Tobacco-free for 6 months Patients remain vulnerable to relapse. Ongoing relapse prevention is needed. Patients who have been tobacco-free for 6 or more months can be classified as former tobacco users. Nevertheless, many remain vulnerable to relapse. The strategies to be applied for former tobacco users are similar to, but less intensive than, those used for recent quitters. The goal for these patients is to remain tobacco-free for life. GOAL: Remain tobacco-free for life.

Quitting is difficult, and tobacco users typically make multiple serious quit attempts before they are able to quit for good. For this reason, clinicians should routinely screen for periodic tobacco use among former users and continue to demonstrate support and encouragement for the patient’s continued success. HERMAN ® is reprinted with permission from LaughingStock Licensing Inc., Ottawa, Canada All rights reserved.

STAGE 4: FORMER TOBACCO USERS
Assess status of quit attempt Slips and relapse Medication compliance, plans for termination Has pharmacotherapy been terminated? Continue to offer tips for relapse prevention Encourage healthy behaviors Congratulate continued success As with recent quitters, clinicians must evaluate the status of the quit attempt. Has the patient had any strong temptations to use tobacco, or any occasional use of tobacco products (even a puff)? Patients might be particularly vulnerable to relapse during times of extreme stress. Also, it is important to ensure that patients are appropriately terminating or tapering off of pharmacotherapy products. Relapse prevention strategies should be discussed as needed, and healthy behaviors should be encouraged—ones that the patient does not associate with tobacco use—such as exercise, hobbies (particularly ones that involve use of the hands), and going to movies with friends. To reduce weight gain, it is important for patients to maintain a healthy diet. Finally, patients who have been off of tobacco for 6 or more months should be congratulated for their enormous success. Staying tobacco-free is a continuous process of learning how to cope with the change. Clinicians should acknowledge, reward, and reinforce the patient’s triumphs in the face of this challenge. Continue to assist throughout the quit attempt. Remember: Behavioral change is a process, not a single step. It’s not uncommon for patients to experience at least one episode of relapse. This should not be regarded as a failure on the part of the patient or the provider, but rather one of the many possible steps within the process of establishing long-term change. Continue to assist throughout the quit attempt.

READINESS to QUIT: A REVIEW
Quit date - 30 days + 6 months This diagram reviews the relationship between the different stages of readiness to quit as a function of time. Not ready to quit Recent quitter Former tobacco user Promote motivation The 5 R’s Behavioral counseling Pharmacotherapy Relapse prevention Behavioral counseling Relapse prevention Ready to quit Behavioral counseling Pharmacotherapy The 5 A’s

COMPREHENSIVE COUNSELING: SUMMARY
Routinely identify tobacco users (ASK) Strongly ADVISE patients to quit ASSESS readiness to quit at each contact Tailor intervention messages (ASSIST) Be a good listener Minimal intervention in absence of time for more intensive intervention ARRANGE follow-up Use the referral process, if needed To summarize the 5 A’s approach (Fiore et al., 2000), clinicians should routinely identify tobacco users, strongly advise patients to quit, and assess stage of readiness to quit at each contact. Patients who are not ready to quit should receive brief motivational interventions (the 5 R’s). In counseling patients, it is imperative that the clinician be a good listener and work with patients in designing treatment plans. When time is limited, a minimal intervention (ask and advise) should be administered. Follow-up is a key component of successful quit attempts. Refer patients to other health care providers, to cessation support groups, or to a toll-free quitline if needed. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

BRIEF COUNSELING: ASK, ADVISE, REFER
Brief interventions have been shown to be effective In the absence of time or expertise: Ask, advise, and refer to other resources, such as local programs or the toll-free quitline QUIT-NOW Brief interventions have been shown to be effective. In a meta-analysis of 17 trials assessing the effects of cessation advice from medical practitioners (Lancaster & Stead, 2004), brief advice was associated with an increased likelihood of quitting (odds ratio, 1.74) versus no advice (or usual care). When time or logistics do not permit comprehensive tobacco cessation counseling during a patient visit, clinicians are encouraged to apply a truncated 5 A’s model, whereby they Ask about tobacco use, Advise tobacco users to quit, and Refer patients who are willing to quit to a telephone quitline or other community-based resource for tobacco cessation. Telephone services that provide tobacco cessation counseling have proliferated over the past decade. These services provide low-cost interventions that can reach patients who might otherwise have limited access to medical treatment, because of geographic location or lack of insurance or financial resources. In clinical trials, telephone counseling services for smoking cessation have been shown to be effective in promoting quitting among the patients who use them (Ossip-Klein & McIntosh, 2003; Stead et al., 2003), and these positive results have been shown to translate into real-world effectiveness (Zhu et al., 2002). Additionally, preliminary evidence suggests that quitlines also are effective for spit tobacco cessation (Severson et al., 2000). With the fall 2004 introduction of a national toll-free quitline number (1-800-QUIT-NOW), all Americans now can receive tobacco cessation counseling at no cost. Even the busiest of clinicians can serve an important role by simply identifying tobacco users and referring them to a quitline for more comprehensive counseling. Lancaster T, Stead L. (2004). Physician advice for smoking cessation. Cochrane Database Syst Rev (4):CD Ossip-Klein DJ, McIntosh S. (2003). Quitlines in North America: Evidence base and applications. Am J Med Sci 326:201–205. Severson HH,et al. (2000). A self-help cessation program for smokeless tobacco users: Comparison of two interventions. Nicotine Tob Res 2:363–370. Stead LF, Lancaster T, Perera R. (2003). Telephone counselling for smoking cessation (Cochrane Review). Cochrane Database Syst Rev (1):CD Zhu SH, et al. (2002). Evidence of real-world effectiveness of a telephone quitline for smokers. N Engl J Med 347:1087–1093. This brief intervention can be achieved in 30 seconds.

WHAT IF… a patient asks you about your use of tobacco?
If a patient asks you whether you use tobacco or have used tobacco in the past, be honest. If you have never been a tobacco user, you really can’t understand how difficult it is to quit. But, being a health care provider, you understand the physiologic and psychosocial nature of addiction—which helps to provide insight. Clinicians counsel patients for all types of diseases without having the diseases themselves. It is appropriate to admit that, while you have not personally experienced quitting yourself, you have worked with plenty of patients who have. Acknowledge that it is a very difficult process. If you have been a tobacco user (or are a current user), then you probably have greater insight into the meaning of tobacco dependence. If you’ve tried to quit before (whether successfully or not), don’t assume that your patients’ experience with quitting will be similar to yours. It may be useful to provide some “this is what happened to me” insight, but don’t express an “I did it, so can you” attitude—this is not a sensitive approach to dealing with patients. Often, some of the best tobacco cessation counselors are individuals who used to use tobacco regularly. Current tobacco users are strongly encouraged to quit.

Sales of tobacco in pharmacies is an important issue that many believe casts a negative light on the pharmacy profession. The reasons that pharmacies cite for selling tobacco have been described as “weak and unconvincing” (Hussar, 2004). Evidence suggests that there is little public or professional support for tobacco sales in pharmacies. For example, in California, only 1.6% of licensed pharmacists (of 1,168 surveyed) and 2.0% of pharmacy students (of 1,518 surveyed) are in favor of tobacco sales in pharmacies. Furthermore, of 988 adult consumers interviewed, 72.3% disagreed with the statement “I am in favor of tobacco products being sold in drugstores,” and 83% stated that if the drugstore where they most commonly shopped were to stop selling tobacco products, they would shop there just as often, 14% would shop there more often, and 3% would shop there less often (Hudmon et al., under review). ♪ Note to instructor(s): Please engage your students in a discussion/debate about whether they believe it is appropriate for pharmacies to sell tobacco. Encourage students to have an opinion on this issue. ♪ Note to instructor(s): Please encourage students who are against tobacco sales in pharmacies to sign our online petition at Hudmon KS, Fenlon CM, Corelli RL, Schroeder SA, Prokhorov AV. (Under review). Tobacco sales in pharmacies: Time to quit. Hussar D. (2004, December 13). Let's get tobacco out of pharmacies! Drug Topics. Retrieved December 31, 2006, from Courtesy of Mell Lazarus and Creators Syndicate. Copyright 2000, Mell Lazarus.

The RESPONSIBILITY of HEALTH PROFESSIONALS
It is inconsistent to provide health care and —at the same time— remain silent (or inactive) about a major health risk. As a final note, it is important to emphasize that it is inconsistent, and perhaps unethical, to provide health care and—at the same time—remain silent (or inactive) about a major health risk. Addressing tobacco use is an essential component of clinical care. Promoting tobacco cessation is, in itself, an important component of therapy—it has immediate payoff in terms of both health improvements and cost savings (Lightwood & Glantz, 1997). The primary goal of the Rx for Change: Clinician-Assisted Tobacco Cessation program is to provide current and future health professionals with the knowledge and skills necessary to make an impact on the incidence of tobacco-related disease in the U.S. and abroad. Clinicians can make a difference (Fiore et al., 2000). Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Lightwood JM, Glantz SA. (1997). Short-term economic and health benefits of smoking cessation: Myocardial infarction and stroke. Circulation 96:1089–1096. TOBACCO CESSATION is an important component of THERAPY.

DR. GRO HARLEM BRUNTLAND, FORMER DIRECTOR-GENERAL of the WHO:
“If we do not act decisively, a hundred years from now our grandchildren and their children will look back and seriously question how people claiming to be committed to public health and social justice allowed the tobacco epidemic to unfold unchecked.” This quote, from Dr. Gro Harlem Bruntland, former Director-General of the World Health Organization, is the closing remark in the 2001 Surgeon General’s report on women and smoking (USDHHS, 2001). It appropriately emphasizes the urgency of the need for clinicians and other health professionals to take a more active role in countering tobacco use. U.S. Department of Health and Human Services (USDHHS). (2001). Women and Smoking: A Report of the Surgeon General. Washington, DC: Public Health Service. USDHHS. (2001). Women and Smoking: A Report of the Surgeon General. Washington, DC: PHS.

AIDS for CESSATION & CASE SCENARIO OVERVIEW
This module focuses on patient education and the proper use of the various aids for tobacco cessation. The information provided in this module derives primarily from the product package inserts. Students should be referred to the Pharmacologic Product Guide during this component of the training. ♪ Note to instructor(s): The following manufacturers’ product-specific web sites are a source of additional important information: ♪ Note to instructor(s): Although the Rx for Change program provides samples of several of the pharmacologic aids for cessation for in-class demonstration (for the pharmacy schools participating in our research study), the hands-on experience with the products is optional. Each instructor and school should decide whether it is appropriate for students to participate in these exercises when active drug is being used (i.e., the nonprescription nicotine replacement therapy agents). Current tobacco users, former tobacco users, and women who are pregnant or breast-feeding should NOT participate in exercises with active drug formulations, because it might be harmful (for current tobacco users and women who are pregnant or breastfeeding) or might lead to relapse (in former tobacco users). Risks associated with these exercises should be clearly indicated to student participants and students who participate in the hands-on experience must remove any active dosage formulations as soon as the manipulation is completed, to avoid exposure to nicotine.

Combination therapy is preferred.
METHODS for QUITTING Nonpharmacologic Pharmacologic There are two basic methods for quitting: Nonpharmacologic Pharmacologic Nonpharmacologic methods primarily involve counseling and behavioral therapies. This includes the provision of social support systems, and problem solving and skills training. As discussed in the Assisting Patients with Quitting module, these methods should be used with all patients attempting to quit using tobacco. Pharmacologic methods approved by the U.S. Food and Drug Administration (FDA) for tobacco cessation include nicotine replacement therapy (NRT), sustained-release bupropion (Zyban) and varenicline (Chantix). Other pharmacologic methods for cessation that are not FDA approved for tobacco cessation are also discussed in this module, as are complementary and alternative therapies. Most tobacco users quit without assistance, and overall, more than 95% of quit attempts end in relapse (CDC, 2002). In general, combination therapy consisting of behavioral counseling with pharmacotherapy is more effective than either method used alone (Fiore et al., 2000). This combined approach is similar to that used in the treatment of other chronic conditions. For example, a diabetic patient may administer insulin in combination with a prescribed diet and exercise regimen. A patient with asthma might use a corticosteroid inhaler in combination with various environmental control measures to prevent asthma exacerbations. Similarly, effective treatment of tobacco use and dependence involves a management plan consisting of behavioral counseling, support, and appropriate pharmacotherapy. Centers for Disease Control and Prevention (CDC). (2002). Cigarette smoking among adults—United States, MMWR 51:642–645. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Combination therapy is preferred.

NONPHARMACOLOGIC METHODS
Cold turkey: Just do it! Unassisted tapering (fading) Reduced frequency of use Lower nicotine cigarettes Special filters or holders Assisted tapering QuitKey Nonpharmacologic methods include the following: Cold turkey: The “simplest” nonpharmacologic method, but the least successful, is cold turkey—the smoker just quits abruptly, without any medication and without tapering off of nicotine. Unassisted tapering: Tobacco users can taper off of tobacco products in a variety of ways. For example, they can self-regulate and reduce the number of cigarettes that they smoke, they can switch to cigarettes with a progressively lower nicotine content (“light” or “ultra-light” cigarettes), or they can purchase special filters or holders that decrease the nicotine inhalation concentration over time. However, many people who use this method smoke fewer cigarettes but still get the same amount of nicotine because they compensate for the low nicotine content by altering the way they smoke. For example, they may inhale more deeply, smoke each cigarette longer, or obstruct the vents on the filters. This method may be a reasonable approach for some smokers to “get ready to quit,” because it disrupts the behavior or habit. However, in general, tapering is not a very effective method of quitting. Scheduled gradual reduction: Products such as the QuitKey (developed and marketed by PICS, Inc.) help patients to quit using tobacco gradually through a computer-assisted behavior modification program.

NONPHARMACOLOGIC METHODS (cont’d)
Formal cessation programs Self-help programs Individual counseling Group programs Telephone counseling 1-800-QUITNOW Web-based counseling Aversion therapy Acupuncture therapy Hypnotherapy Massage therapy Formal cessation programs: An abundance of formal smoking cessation programs are available. These range from self-help manuals to individual and group counseling programs. The National Quitline, launched in 2004 ( QUITNOW), provides all Americans with toll-free telephone-based counseling. For individuals with Internet access, many Web-based programs offer private and convenient (“24/7/365” availability) cessation support. The effectiveness of these types of behavioral programs is enhanced further when pharmacologic agents also are used for cessation. Aversion therapy: This infrequently used approach requires patients to smoke so much that they are nearly nicotine intoxicated, which makes them feel sick and (supposedly) makes them not want cigarettes any more. According to the U.S. Public Health Service Clinical Practice Guideline for treating tobacco use and dependence, aversive smoking interventions may be used with smokers who desire such treatment or who have been unsuccessful using other interventions (Fiore et al., 2000). Alternative and complementary therapies: In recent years many patients have turned to various alternative and complementary therapies for cessation (Villano & White, 2004): The rationale underlying acupuncture therapy is that it releases endorphins, which promote smoking cessation (Villano & White, 2004). One study of 78 patients showed quit rates of 12.5% in the treatment group versus 0% in the placebo group at 6 months (Waite & Clough, 1998). However, the Clinical Practice Guideline (Fiore et al., 2000) does not recommend acupuncture for smoking cessation, and a recent meta-analysis (White et al., 2006) concluded that there is no consistent evidence that acupuncture, acupressure, laser therapy, or electrostimulation are effective. Hypnotherapy also has been used for smoking cessation. Hypnotherapists implant subconscious suggestions to deter smoking. Evidence on its efficacy is conflicting, and currently the evidence is insufficient to support hypnosis as a treatment for smoking cessation (Abbott et al., 2000). Massage therapy is thought to reduce anxiety, decrease stress hormones, and improve mood. In one study, patients used either hand or ear self-massage during tobacco cravings for a period of 1 month. Patients reported improved moods and decreased anxiety, withdrawal symptoms, and number of cigarettes smoked per day (Hernandez-Reif et al., 1999). Massage therapy might be useful as an adjunct therapy to alleviate cravings and anxiety. Abbot NC, Stead LF, White AR, et al. (2000). Hypnotherapy for smoking cessation. Cochrane Database Syst Rev 2:CD Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Hernandez-Reif M, Field T, Hart S. (1999). Smoking cravings are reduced by self-massage. Prev Med 28:28–31. Waite N, Clough JB. (1998). A single-blind, placebo-controlled trial of a simple acupuncture treatment in the cessation of smoking. Br J Gen Pract 48:1487–1490. White AR, Rampes H, Campbell JL. (2006). Acupuncture and related interventions for smoking cessation. Cochrane Database Syst Rev 1:CD Villano LM, White AR. (2004). Alternative therapies for tobacco dependence. Med Clin N Am 88:1607–1621.

SCHEDULED GRADUAL REDUCTION of SMOKING
Gradual reduction of the total number of cigarettes smoked per day Computerized unit facilitates reduction: QuitKey Tapering curve developed based on patient’s smoking level 19–24% abstinent at 1 year Includes telephone counseling support Knowing that pharmacologic aids for cessation may not be appropriate for all patients, clinicians must be knowledgeable about alternative methods for quitting. Some of these methods were discussed earlier. One method of quitting is to gradually reduce the total number of cigarettes smoked per day. This method for cessation can be used by anyone who wants to quit and may be particularly helpful for patients, such as pregnant women, who are not candidates for nicotine replacement or other medications for cessation. This method can involve scheduling the number of cigarettes per day (i.e., written on a calendar), or it can be done using the QuitKey Smoking Cessation Program. The hand-held QuitKey computer assists the smoker in decreasing the frequency of cigarette use over time. Based on data that patients enter during a 1-week baseline period when they smoke “normally,” the computer develops a patient-specific tapering curve appropriate to the patient’s level of smoking. The scheduled gradual reduction concept for smoking cessation has been tested in research studies (Cinciripini et al., 1995, 1997). The QuitKey program, which was developed with funding from the National Institutes of Health, has been tested and proven to be effective in clinical trials (Jerome et al., 1992, 2000; Prue et al., 1990; Riley et al., 2002). The program results in a 19–24% abstinence rate 1 year after quitting. Cinciripini PM, Lapitsky LG, Seay S, Wallfisch A, Kitchens K, Van Vunakis H. (1995). The effects of smoking schedules on cessation outcome: Can we improve on methods of gradual and abrupt nicotine withdrawal? J Consult Clin Psychol 63:388–389. Cinciripini PM, Wetter DW, McClure JB. (1997). Scheduled reduced smoking: Effects on smoking abstinence and potential mechanisms of action. Addict Behav 22:759–767. Jerome A, Fiero PL, Behar A. (2000). Computerized scheduled gradual reduction for smokeless tobacco cessation: Development and preliminary evaluation of a self-help program. Computers in Human Behavior 16:493–505. Jerome A, Perrone R, Kalfus G. (1992). Computer-assisted smoking treatment: A controlled evaluation and long-term follow-up. Journal of Advancement in Medicine 5:29–41. Prue DM, Riley A, Orlandi MA, Jerome A. (1990). Development of a computer-assisted smoking cessation program: A preliminary report. Journal of Advancement in Medicine 3:131–139. Riley W, Jerome A, Behar A, Zack S. (2002). Feasibility of computerized scheduled gradual reduction for adolescent smoking cessation. Substance Use & Misuse 37:277–285.

QuitKey SMOKING CESSATION PROGRAM
This slide diagrams the QuitKey computer, which is lightweight and approximately 2.5 inches long, 1.75 inches wide, and about ½ inch deep. It is designed to be placed on a key ring and is sold with a 3-volt lithium battery that can be replaced. A few key facets of the computer should be pointed out to clarify how it works: The ON-OFF switch is in the lower right corner. The SMOKE button is to the left of the ON-OFF switch and should be depressed each time a cigarette is smoked. The display is digital: On the right is the number of days remaining in each stage of quitting (described in the next slide); on the left is the SMOKE SIGNAL; and at the top is a display of the amount of time until the next scheduled cigarette. On the back of the computer, in the upper right corner, is a START/RESTART button, which must be pressed on the morning of the start date. The button is pressed by pushing the end of a paperclip into the hole. When the button is pressed, a short tune is heard. The button is not to be pressed again during the quitting program. The program is able to adjust the “tapering curve” for smokers who smoke at unscheduled times. When the program repeats a day, the display shows the triangular repeat flag.

QuitKey SMOKING CESSATION PROGRAM
Stage 1 (7 days) Push the SMOKE button every time you smoke, to record smoking habits Turn unit on every morning and off every night Stage 2 (14–34 days) Smoke only when you hear the tone or see the SMOKE SIGNAL; tapers smoking over time Press the SMOKE button every time you smoke The smoking cessation program helps the patient to work through two stages: Stage 1 is the baseline stage. During this stage the computer collects data from the patient to develop the patient’s “curve” for tapering off of cigarettes in Stage 2. To ensure that the tapering curve is appropriate, the patient should be advised to smoke as he or she usually would, during this stage. Each time the smoker lights a cigarette, he or she is to press the SMOKE button. Also, the patient should turn the computer on in the morning upon waking and off at bedtime; this helps the computer to understand the patient’s sleep cycle—which is important, because most smokers don’t smoke during the night. In Stage 2, the QuitKey computer tapers the patient off of cigarettes. The program makes quitting less difficult because it helps the patient to follow the tapered quit plan, as a compliance aid. The patient is to smoke only when he or she hears the tone or sees the SMOKE SIGNAL. Each time the patient smokes, whether or not it is a scheduled smoke, he or she is to press the SMOKE button. And, as with Stage 1, the unit is to be turned on in the morning and off at bedtime. Stage 2 can last between 14 and 34 days, depending on the patient’s smoking habits. By the end of the curve, the smoker should be at ZERO cigarettes per day. Free telephone assistance is available Monday–Friday 9:00 a.m.–6:00 p.m. EST at QUITKEY ( ). ♪ Note to instructor(s): This method for quitting sometimes is criticized, because although the program requires patients to smoke less frequently, they commonly smoke a greater percentage of each cigarette, inhale more deeply, and keep the smoke in their lungs longer, which means they most likely are getting higher levels of nicotine than they are scheduled to receive. However, if patients continue to adhere to the tapering schedule (i.e., smoking a cigarette only when it is scheduled), they eventually will converge on ZERO cigarettes per day. Patients should be encouraged to continue to smoke each cigarette as they normally would (not altering the percentage of cigarette smoked or the depth or length of inhalation). The predecessor of QuitKey is the LifeSign unit. These two hand-held computers use the same methodology; however, the duration of Stage 2 differs. For the LifeSign unit, the duration was 10–28 days, compared to 14–34 days for QuitKey.

SCHEDULED GRADUAL REDUCTION (cont’d)
Who is a candidate for scheduled gradual reduction? Anyone who wants to quit smoking Particularly useful in persons for whom medications might not be a first-line choice, such as pregnant women or teens Spit tobacco users (18.4% abstinent after 1 year) Ordering information or ($59.95) This method for smoking cessation is appropriate for any person who wants to quit smoking. This approach can be particularly useful in patients for whom medications might not be a first-line choice, such as pregnant women or teens (Riley et al., 2002). Smokeless tobacco users also might benefit from this program: When used by spit tobacco users, the program results in a 18.4% abstinence rate after 1 year (Severson et al., 2000). The cost of this program ($59.95 as of June 2006) is less than a full course of NRT or bupropion SR. QuitKey can be ordered on the Internet ( or by calling Riley W, Jerome A, Behar A, Zack S. (2002). Feasibility of computerized scheduled gradual reduction for adolescent smoking cessation. Substance Abuse & Misuse 37:277–285. Severson HH, Akers L, Andrews JA, Lichtenstein E, Jerome A. (2000). Evaluating two self-help interventions for smokeless tobacco cessation. Addict Behav 25:465–470.

PHARMACOTHERAPY “All patients attempting to quit should be encouraged to use effective pharmacotherapies for smoking cessation except in the presence of special circumstances.” The U.S. Public Health Service Clinical Practice Guideline for treating tobacco use and dependence states that “all patients attempting to quit should be encouraged to use effective pharmacotherapies for smoking cessation except in the presence of special circumstances” (Fiore et al., 2000, p. 71). Use of pharmacotherapy requires special consideration in the following patient populations (Fiore et al., 2000): Patients with medical contraindications Patients smoking fewer than 10 cigarettes per day (light smokers) Pregnant or breast-feeding women Adolescents Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Fiore et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS.

PHARMACOLOGIC METHODS: FIRST-LINE THERAPIES
Three general classes of FDA-approved drugs for smoking cessation: Nicotine replacement therapy (NRT) Nicotine gum, patch, lozenge, nasal spray, inhaler Psychotropics Sustained-release bupropion Partial nicotinic receptor agonist Varenicline There are three general classes of FDA-approved drugs for cessation: Nicotine replacement therapy (NRT) includes the nicotine gum, patch, lozenge, nasal spray, and inhaler. A nicotine sublingual tablet currently is available in Europe. The only psychotropic agent currently approved by the FDA for smoking cessation is bupropion SR. Varenicline, a partial nicotinic receptor agonist, was approved by the FDA in 2006 for smoking cessation. According to the U.S. Public Health Service Clinical Practice Guideline for treating tobacco use and dependence, NRT and sustained-release bupropion are considered first-line pharmacotherapies for smoking cessation (Fiore et al., 2000). Varenicline, which was approved six years after the Guideline was published, is not formally classified as a first-line agent although controlled trials suggest it is equal to (Gonzales et al., 2006) or superior to (Jorenby et al., 2006) sustained-release bupropion. Currently, no medications have an FDA indication for use in spit tobacco cessation. ♪ Note to instructor(s): The following pharmacotherapies have been studied but are not recommended by the U.S. Public Health Service Clinical Practice Guideline for treating tobacco use and dependence (Fiore et al., 2000): Anxiolytic agents (buspirone, diazepam) may reduce anxiety associated with nicotine withdrawal, but these agents have not been shown to improve quit rates. Mecamylamine (Inversine) is a central/peripheral nicotinic receptor antagonist. The rationale for its use is that the blockade of the nicotine receptors will prevent the positive reinforcing and pleasurable effects of smoking. Evidence for its use as a smoking cessation aid alone is insufficient. Selective serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline), which may be used to treat withdrawal-associated depression, were not found to be effective in a meta-analysis of five trials (Hughes et al., 2004). Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Gonzales D, Rennard SI, Nides M, et al. (2006). Varenicline, an 4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 296:47-55. Hughes JR, Stead LF, Lancaster. (2004). Antidepressants for smoking cessation. Cochrane Database Syst Rev 4:CD Jorenby DE, Hays JT, Rigotti NA, et al. (2006). Efficacy of varenicline, an 4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 296:56-63. Currently, no medications have an FDA indication for use in spit tobacco cessation.

FDA APPROVALS: SMOKING CESSATION
Rx nicotine inhaler; Rx bupropion SR 2006 2002 Rx transdermal nicotine patch Rx varenicline 1997 ♪ Note to instructor(s): Throughout this module, Rx and OTC are used to indicate prescription and over-the-counter (nonprescription) products, respectively. This slide shows the years when the different pharmacologic agents for smoking cessation received FDA approval: In 1984, the nicotine gum (Nicorette) was the first nicotine replacement product to be approved by the FDA. In 1991, prescription transdermal nicotine patches became available. In 1996, Nicorette gum, Nicoderm CQ patches, and Nicotrol patches (no longer available) became available without a prescription; the prescription nicotine nasal spray (Nicotrol NS) was approved the same year. Bupropion SR (Zyban) was approved in 1997 as the only nonnicotine product to be used as an aid for smoking cessation. The nicotine inhalation system (Nicotrol inhaler) also received FDA approval for prescription use in 1997. The most recent nicotine replacement product to be approved by the FDA is the nicotine lozenge (Commit). This product was approved for nonprescription use in 2002. In 2006, a new class of medications is introduced with the FDA approval of varenicline (Chantix). 1996 Rx nicotine gum OTC nicotine lozenge 1991 OTC nicotine gum & patch; Rx nicotine nasal spray 1984

NRT APPROXIMATELY DOUBLES QUIT RATES.
NRT: RATIONALE for USE Reduces physical withdrawal from nicotine Allows patient to focus on behavioral and psychological aspects of tobacco cessation The rationale for using NRT in tobacco cessation include the following: NRT reduces physical withdrawal symptoms associated with nicotine cessation. NRT increases success by preventing physical nicotine withdrawal symptoms, which are usually experienced following tobacco cessation. NRT allows the patient to focus on behavioral and psychological aspects of tobacco cessation. NRT helps alleviate withdrawal symptoms, allowing the patient to focus on the behavioral and psychological changes necessary for successful tobacco cessation. However, NRT itself can be addicting, and some patients have difficulty terminating its use. NRT use significantly improves the success rates of smoking cessation. A meta-analysis of 103 controlled trials of NRT showed that all products (gum, patch, lozenge, inhaler, and nasal spray) resulted in significantly improved abstinence rates when compared to placebo. Patients using NRT were 1.77 times more likely to successfully quit smoking than were those receiving placebo (Silagy et al., 2004). Advantages of NRT include the following: Patients are not exposed to the carcinogens and other toxic components found in tobacco and tobacco smoke. NRT provides lower, slower, and less variable plasma nicotine concentrations than do cigarettes, which reduces the behaviorally reinforcing effect of smoking. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD NRT APPROXIMATELY DOUBLES QUIT RATES.

NRT: PRODUCTS Polacrilex gum Lozenge Transdermal patch Nasal spray
Nicorette (OTC) Generic nicotine gum (OTC) Lozenge Commit (OTC) Generic nicotine lozenge (OTC) Transdermal patch Nicoderm CQ (OTC) Generic nicotine patches (OTC, Rx) Nasal spray Nicotrol NS (Rx) Inhaler Nicotrol (Rx) Currently available formulations of NRT include gum, lozenge, transdermal patch, nasal spray, and inhaler. The nicotine gum, lozenge, and patch can be purchased without a prescription. The nicotine nasal spray and inhaler require a prescription. To reduce the likelihood of nicotine-related adverse effects, patients should discontinue tobacco use when using these products. Symptoms of nicotine toxicity include headache, nausea and vomiting, abdominal pain, diarrhea, drooling, dizziness, blurred vision, tremor, cold sweat, hypotension, and, in severe cases, respiratory depression.

PLASMA NICOTINE CONCENTRATIONS for NICOTINE-CONTAINING PRODUCTS
Cigarette Moist snuff This graph depicts the plasma venous nicotine concentrations achieved with the various nicotine delivery systems. Peak plasma concentrations are higher and are achieved more rapidly when nicotine is delivered via cigarette smoke compared to the available NRT formulations. Among the NRT formulations, the nasal spray has the most rapid absorption, followed by the gum, lozenge, and inhaler; absorption is slowest with the transdermal formulations. The concentration time curves in this slide depict levels achieved after administration of a single dose of nicotine following a period of overnight abstinence. The administration of nicotine varied across the studies as follows: the cigarette was smoked over 5 minutes, the moist snuff (2 grams Copenhagen) was placed between the check and gum for 30 minutes, the inhaler was used over 20 minutes (80 puffs), the gum was chewed over 30 minutes, the lozenge was held in the mouth for approximately 30 minutes, and the patch was applied to the skin for 1 hour. The data presented in the graph derive from multiple studies and are meant to illustrate the differences between nicotine absorption from tobacco and NRT (Choi et al., 2003; Fant et al., 1999; Schneider et al., 2001). Because NRT formulations deliver nicotine more slowly and at lower levels (e.g., 30–75% of those achieved by smoking), these agents are far less likely to be associated with dependence when compared to tobacco-based products. Choi JH, Dresler CM, Norton MR, Strahs KR. (2003). Pharmacokinetics of a nicotine polacrilex lozenge. Nicotine Tob Res 5:635–644. Fant RV, Henningfield JE, Nelson RA, Pickworth WB. (1999). Pharmacokinetics and pharmacodynamics of moist snuff in humans. Tob Control 8:387–392. Schneider NG, Olmstead RE, Franzon MA, Lunell E. (2001). The nicotine inhaler. Clinical pharmacokinetics and comparison with other nicotine treatments. Clin Pharmacokinet 40:661–684. Time (minutes)

NRT: PRECAUTIONS Patients with underlying cardiovascular disease
Recent myocardial infarction (within past 2 weeks) Serious arrhythmias Serious or worsening angina Some general precautions to consider when recommending the use of NRT as a cessation aid: Nicotine activates the sympathetic nervous system leading to an increase in heart rate, blood pressure, and myocardial contractility. Nicotine may also cause coronary artery vasoconstriction (Benowitz, 2003). These known hemodynamic effects of nicotine have led to concerns about the safety of NRT use in patients with established cardiovascular disease, particularly those with serious arrhythmias, serious or worsening angina, or those patients in the immediate post-myocardial infarction period (within past 2 weeks)(Fiore et al., 2000). Soon after the nicotine patch was approved, anecdotal case reports appeared in the lay press linking NRT use (patch and gum) with adverse cardiovascular events (i.e., arrhythmias, myocardial infarction, stroke). Since then, several randomized, controlled trials have evaluated the safety of NRT in patients with cardiovascular disease including angiographically documented coronary artery stenosis, myocardial infarction, stable angina, and previous coronary artery bypass surgery or angioplasty (Joseph et al., 1996; Tzivoni et al., 1998; Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease, 1994). These trials found no significant increase in the incidence of cardiovascular events or mortality among patients receiving NRT when compared to placebo. However, because the trials specifically excluded patients with unstable angina, serious arrhythmias, and recent myocardial infarction, the Clinical Practice Guideline recommends that NRT be used with caution among patients in the immediate (within 2 weeks) post–myocardial infarction period, those with serious arrhythmias, and those with serious or worsening angina, owing to a lack of safety data in these high-risk populations (Fiore et al., 2000). The use of NRT in patients with cardiovascular disease has been the subject of numerous reviews, and it is widely believed by experts in the field that the risks of NRT in this patient population are small relative to the risks of continued tobacco use (Benowitz, 2003; Benowitz & Gourlay, 1997; Joseph & Fu, 2003; McRobbie & Hajek, 2001; Meine et al., 2005; Silagy et al., 2004). ♪ Note to instructor(s): It is important to emphasize that in patients with NRT precautions, OTC/self-care is not appropriate; NRT must be prescribed by a provider for it to be used. Benowitz NL. (2003). Cigarette smoking and cardiovascular disease: Pathophysiology and implications for treatment. Prog Cardiovasc Dis 46:91–111. Benowitz NL, Gourlay SG. (1997). Cardiovascular toxicity of nicotine: Implications for nicotine replacement therapy. J Am Coll Cardiol 29:1422–1431. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Joseph AM, Fu SS. (2003). Safety issues in pharmacotherapy for smoking in patients with cardiovascular disease. Prog Cardiovasc Dis 45:429–441. Joseph AM, Norman SM, Ferry LH, et al. (1996). The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 335:1792–1798. McRobbie H, Hajek P. (2001). Nicotine replacement therapy in patients with cardiovascular disease: guidelines for health professionals. Addiction 96:1547–1551. Meine TJ, Patel MR, Washam JB, Pappas PA, Jollis JG. (2005). Safety and effectiveness of transdermal nicotine patch in smokers admitted with acute coronary syndromes. Am J Cardiol 15:976–978. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD Tzivoni D, Keren A, Meyler S, et al. (1998). Cardiovascular safety of transdermal nicotine patches in patients with coronary artery disease who try to quit smoking. Cardiovasc Drugs Ther 12:239–244. Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease. (1994). Nicotine replacement therapy for patients with coronary artery disease. Arch Intern Med 154:989–995. NRT products may be appropriate for these patients if they are under medical supervision.

NRT: PRECAUTIONS (cont’d)
Patients with other underlying conditions Active temporomandibular joint disease (gum only) Pregnancy Lactation NRT should be used with caution in the presence of other conditions such as active temporomandibular joint disease (gum only), pregnancy, and lactation: Patients with active temporomandibular joint disease should not use the nicotine gum because doing so might exacerbate their condition. The FDA has classified prescription formulations of nicotine as a pregnancy category D drug, meaning there is evidence of risk to the human fetus. Accordingly, none of the NRT formulations have been FDA approved for use in pregnancy. Although NRT may pose a risk to the developing fetus, some researchers have argued this risk is considerably less than the risks of continued smoking (Benowitz & Dempsey, 2004). However, because it is assumed that NRT can cause fetal harm when administered to pregnant women, NRT during pregnancy should be reserved for women unable to quit using nonpharmacologic methods alone. Pregnant women should use pharmacologic aids for cessation only under the supervision of a physician. Consult with the patient’s obstetrician if needed. According to the U.S. Public Health Service Clinical Practice Guideline for treating tobacco use and dependence, if NRT use is warranted, it is prudent to prescribe doses at the low end of the effective dose range and to consider use of formulations that yield intermittent exposure (e.g., gum, nasal spray, or inhaler) instead of the patch, which provides continuous drug exposure (Fiore et al., 2000). Nicotine and cotinine are secreted in breast milk. In a recent small study, use of the nicotine patch was associated with less exposure to nicotine (compared to smoking) and did not adversely affect milk consumption among breast-feed infants. The investigators concluded that the use of NRT during breast-feeding is safer than continued smoking (Ilett et al., 2003). In a recent review of NRT and breast-feeding, Benowitz & Dempsey (2004) concluded that, among lactating women receiving NRT, the amount of nicotine present in breast milk poses minimal risk to the infant. The authors further argue that exposure to second-hand smoke is far more hazardous to the baby than is the low-level nicotine exposure from NRT (Benowitz & Dempsey, 2004). Although nicotine levels achieved with NRT are less than those achieved with smoking, clinicians should be aware that the nursing infant is at risk for nicotine toxicity, especially if the mother concomitantly smokes and uses NRT. Use of NRT is not approved by the FDA for use in children and adolescents and non-prescription NRT sale is restricted to adults ≥18 years of age. Patients should stop using all forms of tobacco upon initiation of the NRT regimen. Benowitz NL, Dempsey DA. (2004). Pharmacotherapy for smoking cessation during pregnancy. Nicotine Tob Res 6(Suppl. 2):S189–S202. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Ilett KF, Hale TW, Page-Sharp M, et al. (2003). Use of nicotine patches in breast-feeding mothers: Transfer of nicotine and cotinine into human milk. Clin Pharmacol Ther 74:516–524. NRT products may be appropriate for these patients if they are under medical supervision.

NRT: OTHER CONSIDERATIONS
NRT is not FDA-approved for use in children or adolescents Nonprescription sales (patch, gum, lozenge) are restricted to adults ≥18 years of age NRT use in minors requires a prescription Patients should stop using all forms of tobacco upon initiation of the NRT regimen Use of NRT is not approved by the FDA for use in children or adolescents. Non-prescription NRT sales (nicotine patch, gum, lozenge) are restricted to adults ≥18 years of age. NRT use in minors requires a prescription. Patients should stop using all forms of tobacco upon initiation of the NRT regimen.

NICOTINE GUM Nicorette (GlaxoSmithKline); generics
Resin complex Nicotine Polacrilin Sugar-free chewing gum base Contains buffering agents to enhance buccal absorption of nicotine Available: 2 mg, 4 mg; regular, FreshMint, Fruit Chill, mint, & orange flavor FDA approved: 1984 Switched to OTC status: 1996 Available strengths: 2 mg, 4 mg (for persons who smoke heavily) Mint flavor approved: 1998 Generic OTC gum available: 1999 Orange flavor approved: 2000 FreshMint flavor approved: 2005 Fruit Chill flavor approved: 2006 Description of Product Nicotine polacrilex (polé-ah-kril-ex) is a resin complex of nicotine and polacrilin in a sugar-free chewing gum base. The gum has a distinct, tobacco-like, slightly peppery, minty, or citrus taste and contains sorbitol as a sweetener. The Nicorette FreshMint and Fruit Chill formulations are softer to chew than the other formulations. All gum formulations contain buffering agents (sodium carbonate and sodium bicarbonate) to increase salivary pH, thereby enhancing buccal absorption of nicotine. Clinical Efficacy (Silagy et al., 2004) In a meta-analysis of 52 trials, nicotine gum was found to significantly improve quit rates compared to placebo. When data from all trials were pooled, the following long-term (6- to 12-month) abstinence rates were observed: Placebo % Nicotine gum 19.5% The pooled odds ratio of abstinence for nicotine gum was 1.66 (95% CI, 1.52–1.81) relative to placebo. The 4-mg gum is more efficacious than the 2-mg gum as a cessation aid in highly dependent smokers (Fiore et al., 2000). Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD

NICOTINE GUM: DOSING Dosage based on current smoking patterns:
If patient smokes Recommended strength 25 cigarettes/day 4 mg <25 cigarettes/day 2 mg The dosage of nicotine gum is based on the patient’s current level of smoking: Patients who smoke 25 cigarettes a day or more should use the 4-mg strength. Patients who smoke fewer than 25 cigarettes a day should use the 2-mg strength. When the 2-mg gum is used properly, ~0.9 mg of nicotine is absorbed from each piece (Benowitz et al., 1987). Nicotine plasma levels are lower (~8 mg/l) and peak approximately 30 minutes after chewing a 2-mg piece of nicotine gum compared to smoking a single cigarette with peak nicotine levels of ~26 mg/l, which are achieved within 10 minutes (Schneider et al., 1996). In comparison, the average machine-measured yield of nicotine per American cigarette is 0.88 mg (range <0.05 to 2.0 mg) (FTC, 2000). Benowitz NL, Jacob P, Savanapridi C. (1987). Determinants of nicotine intake while chewing nicotine polacrilex gum. Clin Pharmacol Ther 41:467–473. Federal Trade Commission. (2000). “Tar,” nicotine and carbon monoxide of the smoke of 1294 varieties of domestic cigarettes for the year Retrieved December 31, 2006, from Schneider NG, Lunell E, Olmstead RE, Fagerström KO. (1996). Clinical pharmacokinetics of nasal nicotine delivery. A review and comparison to other nicotine systems. Clin Pharmacokinet 31:65–80.

NICOTINE GUM: DOSING (cont’d)
Recommended Usage Schedule for Nicotine Gum Weeks 1–6 Weeks 7–9 Weeks 10–12 1 piece q 1–2 h 1 piece q 2–4 h 1 piece q 4–8 h DO NOT USE MORE THAN 24 PIECES PER DAY. Patients using nicotine gum are more likely to quit successfully if they chew the gum on a fixed schedule rather than as needed (Fiore et al., 2000). This slide shows the manufacturers’ recommended dosing schedule. During the initial 6 weeks of therapy, patients should chew one piece of gum every 1–2 hours while awake. In general, this amounts to at least nine pieces of gum daily. Patients can use additional pieces (up to the daily maximum of 24 pieces per day) if cravings occur between the scheduled doses. In general, persons who smoke heavily will need more pieces to reduce their cravings. Patients will gradually increase the interval between doses using the following schedule: Weeks 7–9: 1 piece every 2–4 hours Weeks 10–12: 1 piece every 4–8 hours ♪ Note to instructor(s): The goal of using nicotine gum is to slowly reduce the dependence on nicotine. The manufacturers’ recommended dosing schedule is designed to reduce nicotine cravings gradually. Strategies recommended by the manufacturers for discontinuing use after 12 weeks of therapy include the following: Chew each nicotine gum piece for only 10–15 minutes, instead of 30 minutes, then gradually begin to reduce the number of pieces used. Chew each piece for longer than 30 minutes and reduce the number of pieces used daily. Substitute ordinary chewing gum for some of the nicotine gum that would normally be used, and increase the number of pieces of ordinary gum while reducing the number of nicotine gum pieces. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

NICOTINE GUM: DIRECTIONS for USE
Chew each piece very slowly several times Stop chewing at first sign of peppery, minty, or citrus taste or slight tingling in mouth (~15 chews, but varies) “Park” gum between cheek and gum (to allow absorption of nicotine across buccal mucosa) Resume slow chewing when taste or tingle fades When taste or tingle returns, stop and park gum in different place in mouth Repeat chew/park steps until most of the nicotine is gone (taste or tingle does not return; generally 30 minutes) Nicotine gum is not like ordinary chewing gum. It is a specially formulated nicotine delivery system that must be chewed properly for optimal results. When chewed like ordinary gum, nicotine will be released rapidly from the polacrilin resin, possibly leading to adverse effects including hiccups, heartburn, or gastric upset. ♪ Note to instructor(s): Instruct students to open the nicotine gum sample and follow along with the directions for use. This is an optional exercise. Current tobacco users, former tobacco users, and women who are pregnant or breast-feeding should not participate in exercises with active drug formulations. Consult with your university or organization to gain approval for the hands-on component of the training. Always use placebo products when possible. Alternatively, distribute pieces of sugarless chewing gum for students to use in practicing the chew-park method. Nicotine gum: Directions for use Chew each piece of gum very slowly several times. Stop chewing at the first sign of peppery taste or slight tingling sensation in the mouth. (This usually happens after about 15 chews, but it varies.) “Park” the gum between the cheek and gum to allow absorption of nicotine across the buccal mucosa (mouth lining). When the taste or tingling dissipates (generally about 1–2 minutes), slowly resume chewing. When the taste or tingling returns, stop chewing and park the gum in a different place in the mouth. Parking the gum in different areas of the mouth will decrease the incidence of mucosal irritation. The chew/park steps should be repeated until most of the nicotine is gone. At this point, the taste or tingling does not return. On average, each piece of gum lasts 30 minutes. ♪ Note to instructor(s): The number of chews necessary for the peppery, minty, or citrus taste or tingling sensation generally ranges from 15 to 30 chews. ♪ Note to instructor(s): Students participating in the gum-chewing exercise should be instructed to discard the gum immediately after experiencing the taste or tingling sensation to avoid adverse effects.

NICOTINE GUM: CHEWING TECHNIQUE SUMMARY
Chew slowly Stop chewing at first sign of peppery taste or tingling sensation The following is a review of proper chewing technique for nicotine gum: Chew slowly. Stop chewing at the first sign of a peppery taste or a tingling sensation. Park the gum between the cheek and gum. Chew again when the peppery taste or tingling sensation fades. Repeat steps 1–4 until most of the nicotine is gone (taste or tingle won’t return; generally about 30 minutes). The health care provider should stress the importance of proper gum chewing technique to increase the likelihood of success with this form of NRT. Chew again when peppery taste or tingle fades Park between cheek & gum

NICOTINE GUM: ADDITIONAL PATIENT EDUCATION
To improve chances of quitting, use at least nine pieces of gum daily The effectiveness of nicotine gum may be reduced by some foods and beverages:  Coffee  Juices  Wine  Soft drinks To improve the chances of quitting, patients should use at least nine pieces of nicotine gum daily (one piece every 1–2 hours). Persons who smoke heavily may need more pieces to reduce their cravings. Emphasize that patients often do not use enough of the gum to derive benefit: They commonly chew too few pieces per day or shorten the length of treatment. For this reason, it may be preferable to recommend a fixed schedule of administration, tapering over 1–3 months (Fiore et al., 2000). The effectiveness of nicotine gum might be reduced by some foods and drinks, such as coffee, juices, wine or soft drinks (Henningfield et al., 1990). Patients should be instructed not to eat or drink for 15 minutes before or while using the nicotine gum. To enhance buccal absorption, nicotine polacrilex is buffered to pH 8.5. Acidic beverages might transiently reduce the pH of the saliva below that which is necessary for optimal buccal absorption of nicotine. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Henningfield JE, Radzius A, Cooper TM, Clayton RR. (1990). Drinking coffee and carbonated beverages blocks absorption of nicotine from nicotine polacrilex gum. JAMA 264:1560–1564. Do NOT eat or drink for 15 minutes BEFORE or while using nicotine gum.

NICOTINE GUM: ADD’L PATIENT EDUCATION (cont’d)
Chewing gum will not provide same rapid satisfaction that smoking provides Chewing gum too rapidly can cause excessive release of nicotine, resulting in Lightheadedness Nausea/vomiting Irritation of throat and mouth Hiccups Indigestion Chewing the gum will not provide the same rapid satisfaction that smoking provides. Recall that buccal absorption of nicotine is far less rapid (peak nicotine concentrations are achieved within 30 minutes), compared to nicotine absorption from cigarette smoking (peak concentrations <10 minutes). Patients should be warned that chewing the gum too rapidly may result in excessive release of nicotine and effects similar to those associated with smoking a cigarette too rapidly or those experienced by nonsmokers when they inhale from a cigarette for the first time: Lightheadedness Nausea and vomiting Irritation of the throat and mouth Hiccups Indigestion

NICOTINE GUM: ADD’L PATIENT EDUCATION (cont’d)
Side effects of nicotine gum include Mouth soreness Hiccups Dyspepsia Jaw muscle ache Nicotine gum may stick to dental work Discontinue use if excessive sticking or damage to dental work occurs Side effects associated with nicotine gum include the following: Mouth soreness Hiccups Dyspepsia Jaw muscle ache These side effects are more common during the first few days of therapy. The consistency of nicotine gum (increased viscosity compared to ordinary chewing gum) may lead to increased adherence to dental work and may not be suitable for patients with the following: Extensive restorations (fillings) Bridges Dentures Caps or crowns Braces If excessive sticking or damage to dental work occurs, patients should discontinue use and consult a dentist.

NICOTINE GUM: SUMMARY ADVANTAGES DISADVANTAGES
Gum use may satisfy oral cravings. Gum use may delay weight gain. Patients can titrate therapy to manage withdrawal symptoms. DISADVANTAGES Gum chewing may not be socially acceptable. Gum is difficult to use with dentures. Patients must use proper chewing technique to minimize adverse effects. Advantages of nicotine gum include the following: Gum use may satisfy oral cravings. Gum use may delay weight gain (Fiore et al., 2000). Patients can titrate therapy to manage withdrawal symptoms. Disadvantages of the gum include the following: Gum chewing may not be socially acceptable. Gum may stick to dental work and dentures. Patients must use proper chewing technique to minimize adverse effects. The gum appears to be particularly helpful with patients who have concerns about postcessation weight gain. The gum also may be advantageous for persons who need to titrate nicotine levels more tightly in order to avoid distraction or irritability withdrawal symptoms that might lead to injury, such as transportation workers or persons who work with heavy machinery. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

NICOTINE LOZENGE Commit (GlaxoSmithKline); generics
Nicotine polacrilex formulation Delivers ~25% more nicotine than equivalent gum dose Sugar-free, mint or cherry flavor (boxed or POP-PAC) Contains buffering agents to enhance buccal absorption of nicotine Available: 2 mg, 4 mg FDA approved for use without a prescription: 2002 Available strengths: 2 mg, 4 mg Generic lozenge available: 2006 Description of Product Nicotine polacrilex (polé-ah-kril-ex) is a resin complex of nicotine and polacrilin in a sugar-free (contains aspartame), light mint or cherry flavored lozenge. The lozenge is meant to be consumed like hard candy or other medicinal lozenges (e.g., sucked and moved from side to side in the mouth until it dissolves). Because the nicotine lozenge dissolves completely, it delivers approximately 25% more nicotine than does an equivalent dose of nicotine gum (Choi et al., 2003). Like the nicotine gum, the lozenge also contains buffering agents (sodium carbonate and potassium bicarbonate) to increase salivary pH, thereby enhancing buccal absorption of the nicotine. Clinical Efficacy (Silagy et al., 2004) In a meta-analysis of four studies using either the nicotine lozenge (nicotine polacrilin) or sublingual tablet (nicotine -cyclodextrin complex; not available in the U.S.), the nicotine lozenge was found to improve quit rates significantly compared to placebo. When data from all trials were pooled, the following long-term (6- to 12-month) abstinence rates were observed: Placebo 8.8% Nicotine lozenge 16.4% The pooled odds ratio of abstinence for the nicotine tablet/lozenge was 2.05 (95% CI, 1.62–2.59) relative to placebo. Choi JH, Dresler CM, Norton MR, Strahs KR. (2003). Pharmacokinetics of a nicotine polacrilex lozenge. Nicotine Tob Res 5:635–644. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD

NICOTINE LOZENGE: DOSING
Dosage is based on the “time to first cigarette” (TTFC) as an indicator of nicotine addiction Use Commit Lozenge 2 mg: If you smoke your first cigarette more than 30 minutes after waking up Unlike other forms of NRT, for which the number of cigarettes smoked per day is used as the basis for dosing, the recommended dosage of the nicotine lozenge is based on the time to first cigarette of the day (TTFC). Some experts believe that the best indicator of nicotine dependence is the need to smoke soon after waking (Heatherton et al., 1989). Based on this method, individuals who smoke their first cigarette of the day within 30 minutes of waking are considered to be more highly dependent on nicotine than are those who smoke their first cigarette more than 30 minutes after waking. Because the nicotine lozenge has been studied in clinical trials using the TTFC as a dosage selector, the product is licensed for use in the following manner: Patients who smoke their first cigarette of the day within 30 minutes of waking should use the 4-mg strength. Patients who smoke their first cigarette of the day more than 30 minutes after waking should use the 2-mg strength. Heatherton TF, Kozlowski LT, Frecker RC, et al. (1989). Measuring the heaviness of smoking: Using self-reported time to the first cigarette of the day and number of cigarettes smoked per day. Br J Addict 84:791–799. Use Commit Lozenge 4 mg: If you smoke your first cigarette of the day within 30 minutes of waking up

NICOTINE LOZENGE: DOSING (cont’d)
Recommended Usage Schedule for Commit Lozenge Weeks 1–6 Weeks 7–9 Weeks 10–12 1 lozenge q 1–2 h q 2–4 h q 4–8 h DO NOT USE MORE THAN 20 LOZENGES PER DAY. Patients using the nicotine lozenge are more likely to quit successfully if they use the lozenge on a fixed schedule rather than as needed. This slide shows the manufacturer’s recommended dosing schedule. During the initial 6 weeks of therapy, patients should suck on one lozenge every 1–2 hours (while awake). In general, this amounts to at least nine lozenges daily. Patients can use additional lozenges (up to 5 lozenges in 6 hours or a maximum of 20 lozenges per day ) if cravings occur between the scheduled doses. Patients should gradually increase the interval between doses using the following schedule: Weeks 7–9: 1 lozenge every 2–4 hours Weeks 10–12: 1 lozenge every 4–8 hours ♪ Note to instructor(s): The goal of using the nicotine lozenge is to slowly reduce the dependence on nicotine. The manufacturer’s recommended dosing schedule will help reduce nicotine cravings gradually.

NICOTINE LOZENGE: DIRECTIONS for USE
Use according to recommended dosing schedule Place in mouth and allow to dissolve slowly (nicotine release may cause warm, tingling sensation) Do not chew or swallow lozenge. Occasionally rotate to different areas of the mouth. Lozenge will dissolve completely in about 2030 minutes. The nicotine lozenge is a specially formulated nicotine delivery system that must be used properly for optimal results. Although the nicotine lozenge is used like hard candy or other medicinal lozenges, if patients chew or swallow the lozenge or consume too many in a short period of time, they are more likely to experience adverse effects. Nicotine lozenge: Directions for use The lozenge should be used on a regular basis to reduce nicotine cravings and other withdrawal symptoms. Allow the lozenge to dissolve slowly. When nicotine is released from the polacrilin resin, the patient may experience a warm, tingling sensation. To reduce the risk of gastrointestinal side effects, the lozenge should not be chewed or swallowed. The patient should occasionally rotate the lozenge to different areas of the mouth to minimize the potential for mucosal irritation. On average, the lozenge will dissolve completely within 20–30 minutes. ♪ Note to instructor(s): The image depicts the size of the nicotine lozenge in comparison to a dime.

NICOTINE LOZENGE: ADDITIONAL PATIENT EDUCATION
To improve chances of quitting, use at least nine lozenges daily during the first 6 weeks The lozenge will not provide the same rapid satisfaction that smoking provides The effectiveness of the nicotine lozenge may be reduced by some foods and beverages:  Coffee  Juices  Wine  Soft drinks To improve the chances of quitting, patients should use at least nine nicotine lozenges daily (one every 1–2 hours) during the first 6 weeks of treatment. The nicotine lozenge will not provide the same rapid satisfaction that smoking provides. Peak nicotine concentrations achieved for the lozenge range from 30 to 60 minutes (Choi et al., 2003) and are significantly prolonged compared to cigarette smoking (peak concentrations <10 minutes). The effectiveness of the nicotine lozenge may be reduced by some foods and beverages, such as coffee, juices, wine, or soft drinks. Patients should be instructed not to eat or drink for 15 minutes before or while using the nicotine lozenge. To enhance buccal absorption, nicotine polacrilex is buffered to an alkaline pH. Acidic beverages might transiently reduce the pH of the saliva below that which is necessary for optimal buccal absorption of nicotine. Choi JH, Dresler CM, Norton MR, Strahs KR. (2003). Pharmacokinetics of a nicotine polacrilex lozenge. Nicotine Tob Res 5:635–644. Do NOT eat or drink for 15 minutes BEFORE or while using the nicotine lozenge.

NICOTINE LOZENGE: ADD’L PATIENT EDUCATION (cont’d)
Side effects of the nicotine lozenge include Nausea Hiccups Cough Heartburn Headache Flatulence Insomnia Side effects associated with the nicotine lozenge include the following: Nausea Hiccups Cough Heartburn Headache Flatulence Insomnia Patients who use more than one lozenge at a time, continuously use one lozenge after another, or chew or swallow the lozenge are more likely to experience heartburn or indigestion.

NICOTINE LOZENGE: SUMMARY
ADVANTAGES Lozenge use may satisfy oral cravings. The lozenge is easy to use and conceal. Patients can titrate therapy to manage withdrawal symptoms. DISADVANTAGES Gastrointestinal side effects (nausea, hiccups, and heartburn) may be bothersome. Advantages of nicotine lozenge include the following: Lozenge use may satisfy oral cravings. The lozenge is easy to use and conceal. Patients can titrate therapy to manage withdrawal symptoms. Disadvantages of the gum include the following: Gastrointestinal side effects (nausea, hiccups, and heartburn) may be bothersome.

TRANSDERMAL NICOTINE PATCH Nicoderm CQ (GlaxoSmithKline); generic
Nicotine is well absorbed across the skin Delivery to systemic circulation avoids hepatic first-pass metabolism Plasma nicotine levels are lower and fluctuate less than with smoking FDA approved: 1991 Available OTC: 1996 Description of Product Transdermal nicotine delivery systems consist of an impermeable surface layer, a nicotine reservoir, an adhesive layer, and a removable protective liner. The technology for delivery of nicotine across the skin varies by manufacturer. Nicoderm uses a rate-controlling membrane. The generic patches (previously marketed as Habitrol) use drug-dispersion-type systems whereby release of nicotine is controlled by diffusion of the drug across an adhesive layer (Gore & Chien, 1998). Clinical Efficacy (Silagy et al., 2004) In a meta-analysis of 37 trials, the nicotine transdermal patch was found to significantly improve quit rates compared to placebo. When data from all trials were pooled, the following long-term (6- to 12-month) abstinence rates were observed: Placebo % Nicotine patch 14.6% The pooled odds ratio of abstinence for the transdermal nicotine patch was 1.81 (95% CI, 1.63–2.02) relative to placebo. The nicotine in the patch is well absorbed across the skin. The delivery of nicotine to the systemic circulation avoids hepatic first-pass metabolism. Plasma nicotine concentrations from the patch are lower and fluctuate less than do those achieved with tobacco products. Plasma nicotine levels obtained via transdermal delivery are approximately 50% lower than those achieved with cigarette smoking. Lower levels of nicotine still alleviate the symptoms of withdrawal but are far less likely to lead to dependence when compared to tobacco or other forms of NRT (Gore & Chien, 1998). In pharmacokinetic evaluations, the onset of nicotine absorption from the various transdermal formulations was 1–4 hours. Similarly, the time to reach maximal plasma levels ranged from 3 to 12 hours following application (Palmer et al., 1992). Gore AV, Chien YW. (1998). The nicotine transdermal system. Clin Dermatol 16:599–615. Palmer KJ, Buckley MM, Faulds D. (1992). Transdermal nicotine: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation. Drugs 44:498–529. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD

TRANSDERMAL NICOTINE PATCH: PREPARATION COMPARISON
Product Nicoderm CQ Generic Nicotine delivery 24 hours Availability OTC Rx/OTC Strengths 7-mg patch 14-mg patch 21-mg patch Products Available Nicoderm CQ PatchOTC (GlaxoSmithKline) Switched to OTC status: August 1996 Availability: 7 mg, 14 mg, 21 mg (24-hour nicotine delivery system); also available in a clear formulation Generic nicotine patchRx,OTC (formerly Habitrol Transdermal System) Manufacturers: OTC product (Novartis Consumer Health) Rx product (Watson Pharmaceuticals) Available OTC: November 1999 Availability: 7 mg, 14 mg, 21 mg (24-hour nicotine delivery system) ♪ Note to instructor(s): Novartis manufactures the OTC product but has sold the rights to a private- label company that is responsible for marketing and distributing the product for various retail pharmacies (e.g., Albertsons, CVS, Duane Reade, Kroger, Longs, Medicine Shoppe, Rite-Aid, Safeway, Walgreens, Wal-Mart). The product is labeled as Nicotine Transdermal System Step 1, Step 2, and Step 3. ♪ Note to instructor(s): Previously, Pfizer marketed the Nicotrol transdermal patch (5 mg, 10 mg, 15 mg; 16-hour nicotine delivery systems). This patch formulation was discontinued in 2005 and is no longer commercially available. Additionally, a fourth nicotine transdermal patch (11 mg, 22 mg; 24-hour nicotine delivery systems) utilizing a nontapering 6-week regimen was available. The prescription product was originally marketed as Prostep (Lederle). In December 1998 the product was switched to OTC status and distributed to drug stores, grocery stores, and discount stores under a private label. This patch formulation was discontinued in 2003 and is no longer commercially available.

TRANSDERMAL NICOTINE PATCH: DOSING
Product Light Smoker Heavy Smoker Nicoderm CQ 10 cigarettes/day Step 2 (14 mg x 6 weeks) Step 3 (7 mg x 2 weeks) >10 cigarettes/day Step 1 (21 mg x 6 weeks) Step 2 (14 mg x 2 weeks) Generic (formerly Habitrol) Step 1 (21 mg x 4 weeks) The dosing schedules for the nicotine patches vary. In general, persons who smoke heavily require higher doses of nicotine. Although each of the currently marketed formulations uses a tapering course of therapy, no evidence indicates that gradual weaning is more effective than abrupt discontinuation (Silagy et al., 2004). Furthermore, 8 weeks of treatment appears to be as efficacious as longer durations (Silagy et al., 2004). When patches applied for 16 hours (e.g., the formerly-available Nicotrol patch) were compared to patches applied for 24 hours, no significant differences were found in quit rates (Silagy et al., 2004). However, one study found that patients with strong morning cravings for cigarettes might have more success with a patch applied for 24 hours (Shiffman et al., 2000). ♪ Note to instructor(s): Some students might ask about use of higher than recommended doses of transdermal nicotine for persons who smoke heavily. High-dose transdermal nicotine (44–63 mg/day) appears to be safe (Benowitz et al., 1998; Dale et al., 1995; Fredrickson et al., 1995; Hurt et al., 2003; Bars et al., 2006). However, trials evaluating higher doses of NRT have yielded conflicting results. Some studies suggest higher doses of NRT may be more effective in heavy smokers (Dale et al., 1995; Tonnesen et al., 1999; Bars et al., 2006), whereas others have demonstrated slight but not statistically significant improvements in cessation rates (Hughes et al., 1999; Jorenby et al., 1995) or no difference (Killen et al., 1999; Paoletti et al., 1996). When the results of six studies were pooled, the odds ratio for abstinence was 1.21 (95% CI, 1.03–1.42), suggesting high-dose NRT therapy may be advantageous in some patients (Silagy et al., 2004). This approach should be reserved for patients not able to quit using conventional doses of transdermal NRT. Bars MP, Banauch GI, Appel D, Andreachi M, Mouren P et al. (2006). "Tobacco Free With FDNY": the New York City Fire Department World Trade Center Tobacco Cessation Study. Chest 129: Benowitz NL, Zevin S, Jacob P, 3rd. (1998). Suppression of nicotine intake during ad libitum cigarette smoking by high-dose transdermal nicotine. J Pharmacol Exp Ther 287:958–962. Dale LC, Hurt RD, Offord KP, Lawson GM. (1995). High-dose nicotine patch therapy; percentage of replacement and smoking cessation. JAMA 274:1353–1358. Fredrickson PA, Hurt RD, Lee GM, et al. (1995). Safety and tolerability of high dose transdermal nicotine therapy for heavy smokers. Psychopharmacology 122:215–222. Hughes JR, Lesmes GR, Hatsukami DK, et al. (1999). Are higher doses of nicotine replacement more effective for smoking cessation? Nicotine Tob Res 1:169–174. Hurt RD, Krook JE, Croghan IT, et al. (2003). Nicotine patch therapy based on smoking rate followed by bupropion for prevention of relapse to smoking. J Clin Oncol 21:914–920. Jorenby D, Smith SS, Fiore MC, et al. (1995). Varying nicotine patch dose and type of smoking cessation counseling. JAMA 274:1347–1352. Killen JD, Fortmann SP, Davis L, Strausberg L, Varady A. (1999). Do heavy smokers benefit from higher dose nicotine patch therapy? Exp Clin Psychopharmacol 7:226–233. Paoletti P, Fornai E, Maggiorelli F, Puntoni R, Viegi G, et al. (1996). Importance of baseline cotinine plasma values in smoking cessation: Results from a double-blind study with nicotine patch. Eur Respir J 9:643–651. Shiffman S, Elash CA, Paton SM, et al. (2000). Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving. Addiction 95:1185–1195. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD Tonnesen P, Paoletti P, Gustavsson G, et al. (1999). Higher dosage nicotine patches increase one-year smoking cessation rates: Results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Eur Respir J 13:238–246.

TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE
Choose an area of skin on the upper body or upper outer part of the arm Make sure skin is clean, dry, hairless, and not irritated Apply patch to different area each day Do not use same area again for at least 1 week ♪ Note to instructor(s): Instruct students to remove the sample nicotine patch from the foil pouch and follow along with the directions for use. This is an optional exercise. Current tobacco users, former tobacco users, and women who are pregnant or breast-feeding should not participate in exercises with active drug formulations. Consult with your university or organization to gain approval for the hands-on component of the training. Always use placebo products when possible. Alternatively, distribute samples of the nicotine patch for students to handle but not apply. ♪ Note to instructor(s): Before distributing the patches during class, it is helpful to make a horizontal cut across the upper corner of the patch with scissors or clippers. This will allow the students to quickly open the foil pouch during class. If this step is not performed before class, participants might be unable to open the child-resistant foil pouches. Transdermal nicotine patch: Directions for use Choose an area of skin on the upper body or the upper outer part of the arm. To ensure that the patch will adhere well, make sure the skin is nonhairy, clean (not oily), dry, and free of creams, lotions, oils, or powder. Do not apply the patch to skin that is inflamed, burned, broken out, or irritated in any way. These conditions may alter the amount of drug absorbed. The patch should be applied to a different area each day. To minimize the potential for local skin reactions, the same area should not be used again for at least 1 week.

TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE (cont’d)
Remove patch from protective pouch Transdermal nicotine patch: Directions for use (cont’d) Remove the patch from the protective pouch (save pouch for later disposal of used patch). ♪ Note to instructor(s): The appearance of the transdermal patch will be slightly different for each manufacturer.

Peel off half of the backing from patch Transdermal nicotine patch: Directions for use (cont’d) Remove half of the protective liner from the patch. Try not to touch the exposed adhesive (i.e., the sticky side) because nicotine on hands can get into the eyes or nose and cause stinging or redness.

Apply adhesive side of patch to skin Peel off remaining protective covering Press firmly with palm of hand for 10 seconds Make sure patch sticks well to skin, especially around edges Transdermal nicotine patch: Directions for use (cont’d) Immediately apply the sticky side of the patch to the skin. Peel off the remaining half of the protective covering. Press the patch firmly on the skin with the palm of the hand for 10 seconds. Make sure the patch sticks well to the skin, especially around the edges. This is necessary to ensure a good seal.

Wash hands: Nicotine on hands can get into eyes or nose and cause stinging or redness Do not leave patch on skin for more than 24 hours— doing so may lead to skin irritation Adhesive remaining on skin may be removed with rubbing alcohol or acetone Dispose of used patch by folding it onto itself, completely covering adhesive area Transdermal nicotine patch: Directions for use (cont’d) Wash hands after patch application because nicotine on hands could get into the eyes or nose and cause stinging or redness. After 24 hours, remove the old patch. The patch should not be left on the skin for more than 24 hours, because this may lead to skin irritation. Any adhesive remaining on the skin may be removed with rubbing alcohol or acetone. Dispose of a used patch by folding it onto itself, completely covering the adhesive area.

TRANSDERMAL NICOTINE PATCH: ADDITIONAL PATIENT EDUCATION
Water will not harm the nicotine patch if it is applied correctly; patients may bathe, swim, shower, or exercise while wearing the patch Do not cut patches to adjust dose Nicotine may evaporate from cut edges Patch may be less effective Keep new and used patches out of the reach of children and pets Remove patch before MRI procedures Water will not harm the nicotine patch if it is applied correctly. Patients may bathe, swim, shower, or exercise while wearing the patch. Due to the high cost of nicotine patches, patients will often try to economize by cutting patches in half to save money. It is important to tell patients that they should not cut patches to adjust the dose. Nicotine in the patch may evaporate from the cut edges and the patch may be less effective. Keep new and used patches out of the reach of children and pets. Burns from nicotine patches worn during an MRI have been reported, likely caused by the metallic component in the backing of some patches (Institute for Safe Medical Practices, 2004) Institute for Safe Medical Practices. (2004, April 8). Burns in MRI patients wearing transdermal patches. Medication Safety Alert! 9(7). Retrieved December 31, 2006, from

TRANSDERMAL NICOTINE PATCH: ADD’L PATIENT EDUCATION (cont’d)
Side effects to expect in first hour: Mild itching Burning Tingling Additional possible side effects: Vivid dreams or sleep disturbances Headache Shortly after applying the nicotine patch, patients may experience the following side effects: Mild itching Burning Tingling These effects are normal and should resolve within an hour. Additional possible side effects include the following: Vivid dreams or sleep disturbances. Patients should be advised to remove the patch at bedtime if this side effect becomes troublesome. Headache

TRANSDERMAL NICOTINE PATCH: ADD’L PATIENT EDUCATION (cont’d)
After patch removal, skin may appear red for 24 hours If skin stays red more than 4 days or if it swells or a rash appears, contact health care provider—do not apply new patch Local skin reactions (redness, burning, itching) Usually caused by adhesive Up to 50% of patients experience this reaction Fewer than 5% of patients discontinue therapy Avoid use in patients with dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis) After removal, the skin under the patch may appear red for the next 24 hours. If a skin rash develops after the use of a nicotine patch, or if the skin under the patch becomes swollen or very red, the patient should contact a health care provider. The patient should not apply a new patch. Local skin reactions (redness, burning, itching) These reactions are usually caused by irritation resulting from skin occlusion or from a response to the adhesives. Up to 50% of patients experience these reactions. Less than 5% of patients discontinue therapy: Make certain patient is rotating patch application sites. Consider different brand of patch. Each manufacturer uses different adhesives. Consider treating skin reactions with OTC hydrocortisone cream (1%) or oral antihistamines. Patients with dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis) are more likely to experience skin irritation and should not use the nicotine patch.

TRANSDERMAL NICOTINE PATCH: SUMMARY
ADVANTAGES The patch provides consistent nicotine levels. The patch is easy to use and conceal. Fewer compliance issues are associated with patch use. DISADVANTAGES Patients cannot titrate the dose. Allergic reactions to the adhesive may occur. Patients with dermatologic conditions should not use the patch. Advantages of the nicotine patch include the following: Steady-state nicotine levels are achieved throughout the day. The patch is easy to use and conceal. Fewer compliance issues are associated with the patch. Disadvantages of the patch include the following: Patients cannot titrate the dose. Allergic reactions to the adhesive may occur. Patients with underlying dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis) should not use the patch because they are more likely to experience skin irritation.

NICOTINE NASAL SPRAY Nicotrol NS (Pfizer)
Aqueous solution of nicotine in a 10-ml spray bottle Each metered dose actuation delivers 50 µl spray 0.5 mg nicotine ~100 doses/bottle Rapid absorption across nasal mucosa FDA approved: March 1996 (prescription only) Description of Product Nicotrol NS (nicotine nasal spray) is an aqueous solution of nicotine available in a metered-spray pump for administration to the nasal mucosa. Each actuation delivers a metered 50-µL spray containing 0.5 mg of nicotine. Each bottle contains approximately 100 doses (200 sprays) or about a 1-week supply (about 15 doses per day). Nicotine is absorbed rapidly, and plasma nicotine concentrations attained via the nasal spray are comparable to (but lower than) those achieved by smoking. The nasal spray has a faster onset of action (tmax 11–13 minutes) compared to the gum, patch, or inhaler (Schneider et al., 1996). Clinical Efficacy (Silagy et al., 2004) In a meta-analysis of four trials, the nicotine nasal spray was found to improve quit rates significantly compared to placebo. When data from all trials were pooled, the following long-term (6- to 12-month) abstinence rates were observed: Placebo 11.8% Nicotine nasal spray 23.9% The pooled odds ratio of abstinence for the nicotine nasal spray was 2.35 (95% CI, 1.63–3.38) relative to placebo. Schneider NG, Lunell E, Olmstead RE, Fagerström KO. (1996). Clinical pharmacokinetics of nasal nicotine delivery. A review and comparison to other nicotine systems. Clin Pharmacokinet 31:65–80. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD

NICOTINE NASAL SPRAY: DOSING & ADMINISTRATION
One dose = 1 mg nicotine (2 sprays, one 0.5 mg spray in each nostril) Start with 1–2 doses per hour Increase prn to maximum dosage of 5 doses per hour or 40 mg (80 sprays; ~½ bottle) daily For best results, patients should use at least 8 doses daily for the first 6–8 weeks Termination: Gradual tapering over an additional 4–6 weeks Patients should be instructed to stop smoking completely while using the nicotine nasal spray. One dose is 1 mg of nicotine—two sprays, one (0.5 mg spray) in each nostril. The recommended starting regimen is one or two doses per hour for 6–8 weeks. This may be increased up to a maximum recommended dose of 40 mg/day (80 sprays, about half a bottle). For best results, patients should be encouraged to use at least the recommended minimum of 8 doses per day during the first 6–8 weeks of therapy. Less frequent administration may be less effective. After 6–8 weeks, the dose should be decreased gradually over an additional 4–6 weeks. ♪ Note to instructor(s): No tapering strategy has been shown to be optimal in clinical studies. Many patients simply stopped using the spray at their last clinic visit. Strategies recommended by the manufacturer for discontinuing use include the following: Use only half a dose (one spray) at a time. Use the spray less frequently: Skip a dose by not medicating every hour. Keep a tally of daily usage, and try to meet a steadily reducing usage target.

NICOTINE NASAL SPRAY: DIRECTIONS for USE
Press in circles on sides of bottle and pull to remove cap ♪ Note to instructor(s): Demonstrate for students, using nicotine nasal spray sample or placebo. Pass around sample for class to see and handle. Students should NOT use this prescription product. Nicotine nasal spray: Directions for use Remove the cap. Using your thumb and index finger, press in on the circles on the sides of the bottle. Pull off the cap. Note: This child-resistant cap can be very difficult to remove. It is important to press firmly on the circles on the side of the bottle to unlock the cap.

NICOTINE NASAL SPRAY: DIRECTIONS for USE (cont’d)
Prime the pump (before first use) Obtain facial tissue or paper towel Hold bottle and press on bottom with thumb Pump into tissue until fine spray is observed (6–8 times) If pump is not used for 24 hours, prime the pump 1–2 times Nicotine nasal spray: Directions for use (cont’d) Before using the nasal spray for the first time, the pump must be primed. This is done by actuating the device into a tissue: Obtain a facial tissue or paper towel. Hold the bottle and press firmly on the glass bottom of the unit with thumb. Pump into the tissue until a fine spray is visible (about 6–8 times). The tissue should be discarded after use. If the pump is not used for 24 hours, it should be primed into a tissue 1–2 times. To minimize drug wastage, avoid excessive priming.

Blow nose (if not clear) Tilt head back slightly and insert tip of bottle into nostril as far as comfortable Breathe through mouth, and spray once in each nostril Do not sniff or inhale while spraying Nicotine nasal spray: Directions for use (cont’d) Before using the spray, blow nose if it is not clear. Tilt head back slightly and insert the tip of the bottle into the nostril as far as is comfortable. Breathe through the mouth, and spray once in each nostril. Do not sniff, swallow, or inhale through the nose while administering the medication because this increases the irritating effects of the spray.

If nose runs, gently sniff to keep nasal spray in nose Wait 2–3 minutes before blowing nose Wait 5 minutes before driving or operating heavy machinery (spray may cause tearing, coughing, and sneezing) Avoid contact with skin, eyes, and mouth If contact occurs, rinse with water immediately Nicotine is absorbed through skin and mucous membranes Nicotine nasal spray: Directions for use (cont’d) If nose runs, gently sniff to keep nasal spray in the nose. Wait 2–3 minutes before blowing nose to allow the nicotine to be absorbed across the nasal mucosa. Place the cap back on the bottle after use. Because of the potential for tearing, coughing, and sneezing, wait 5 minutes before driving or operating heavy machinery. Avoid contact with skin, eyes, and mouth. If contact occurs, rinse immediately with water, because nicotine is readily absorbed across the skin and mucous membranes.

NICOTINE NASAL SPRAY: ADDITIONAL PATIENT EDUCATION
What to expect (first week): Hot peppery feeling in back of throat or nose Sneezing Coughing Watery eyes Runny nose Side effects should lessen over a few days Regular use during the first week will help in development of tolerance to the irritant effects of the spray If side effects do not decrease after a week, contact health care provider What to expect during first week: Hot peppery feeling in the back of the throat or nose Sneezing Coughing Watery eyes Runny nose These adverse effects should lessen over a few days. Regular use during the first week will help the patient adapt to the irritant effects of the spray. Some investigators have found that with regular use during the first week, tolerance to the irritant effects of the spray develops (Benowitz et al., 1997). However, the irritant effects of the spray should not be minimized because nasal or airway reactions are common (Fiore et al., 2000): 94% of patients report moderate-to-severe irritation in the first 2 days of therapy. 81% still report nasal irritation (mild to moderate) after 3 weeks. If side effects do not lessen after a week, the patient should contact his or her health care provider. Benowitz NL, Zevin S, Jacob P. (1997). Sources of variability in nicotine and cotinine levels with use of nicotine nasal spray, transdermal nicotine and cigarette smoking. Br J Clin Pharmacol 43;259–267. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

NICOTINE NASAL SPRAY: SUMMARY
ADVANTAGES Patients can easily titrate therapy to rapidly manage withdrawal symptoms. DISADVANTAGES Nasal/throat irritation may be bothersome. Nasal spray has higher dependence potential. Patients with chronic nasal disorders or severe reactive airway disease should not use the spray. Advantages of the nicotine nasal spray include the following: The dose can be easily titrated to rapidly manage withdrawal symptoms. Disadvantages of the nasal spray include the following: The initial nasal or throat irritation can be bothersome; it may take up to 3 weeks for the patient to tolerate therapy. The nicotine nasal spray has a higher dependence potential relative to other NRT formulations but a lower dependence potential relative to tobacco products. About 15–20% of patients continue to use the nicotine nasal spray for longer periods than recommended (6–12 months), and 5% use the spray at higher doses than recommended (Fiore et al., 2000). Patients with chronic nasal disorders (e.g., rhinitis, polyps, sinusitis) or patients with severe reactive airway disease should not use the nicotine nasal spray because of the irritant effects of the spray. Asthma exacerbation has been noted in some patients after administration of nicotine nasal spray. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

NICOTINE INHALER Nicotrol Inhaler (Pfizer)
Nicotine inhalation system consists of Mouthpiece Cartridge with porous plug containing 10 mg nicotine Delivers 4 mg nicotine vapor, absorbed across buccal mucosa May satisfy hand-to-mouth ritual of smoking FDA approved: May 1997 (prescription only) Description of Product The Nicotrol Inhaler (nicotine inhalation system) consists of a mouthpiece and a plastic cartridge delivering 4 mg of nicotine as an inhaled vapor from a porous plug containing 10 mg of nicotine and 1 mg of menthol. Menthol is added to decrease the irritant effects of nicotine (Schneider et al., 2001). Given that the usual pack-a-day smoker repeats the hand-to-mouth motion up to 200 times per day or 73,000 times each year, it is not surprising that many smokers find they miss the physical manipulation of the cigarette and associated behaviors that go with smoking. The nicotine inhaler was designed to provide nicotine replacement in a manner similar to smoking while addressing the sensory and ritualistic factors important to many smokers (Schneider et al., 2001). As a patient puffs on the inhaler mouthpiece, buccal nicotine vapor is released and delivers nicotine to the mouth and throat, where it is absorbed through the mucosa. Less than 5% of the nicotine in a dose reaches the lower respiratory tract. With an intensive inhalation regimen (80 puffs over 20 minutes), about 4 mg of nicotine is delivered and, of that, 2 mg is absorbed. Plasma nicotine levels are 50–70% lower than those achieved with cigarette smoking, and peak nicotine concentrations occur after 30 minutes, compared to 5 minutes after cigarette smoking (Schneider et al., 2001). Clinical Efficacy (Silagy et al., 2004) In a meta-analysis of four trials, the nicotine oral inhaler was found to significantly improve quit rates compared to placebo. When data from all trials were pooled, the following long-term (6- to 12-month) abstinence rates were observed: Placebo 9.1% Nicotine inhaler 17.1% The pooled odds ratio of abstinence for the nicotine inhaler was 2.14 (95% CI, 1.44–3.18) relative to placebo. Schneider NG, Olmstead RE, Franzon MA, Lunell E. (2001). The nicotine inhaler. Clinical pharmacokinetics and comparison with other nicotine treatments. Clin Pharmacokinet 40:661–684. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD

NICOTINE INHALER: DOSING
Start with 6 cartridges/day Increase prn to maximum of 16 cartridges/day Use for minimum of 3 weeks, maximum of 12 weeks Gradual dosage reduction: if needed over additional 6–12 weeks The initial dose for the inhaler should be individualized. Patients should titrate the dose to the level of nicotine that alleviates withdrawal symptoms. The best effects are achieved by frequent continuous puffing (20 minutes). In clinical trials, the average daily dose was more than 6 cartridges (range 3–18) for patients who successfully quit smoking. Patients should start with at least 6 cartridges per day and increase as needed to a maximum of 16 cartridges per day for 3–12 weeks. The recommended duration of treatment is 3 months (minimum, 3 weeks recommended), after which patients may be weaned from the inhaler by gradual reduction of the daily dose over the following 6–12 weeks. The safety and efficacy of the continued use of nicotine inhaler for periods longer than 6 months have not been studied, and such use is not recommended. Dosing recommendations are summarized below: Duration Recommended cartridges/day Initial treatment Up to 12 weeks 6–16 Gradual reduction 6–12 weeks No tapering strategy has been (if needed) shown to be superior to any other in clinical studies. ♪ Note to instructor(s): Most patients will need to gradually discontinue using the nicotine inhaler after the initial treatment period. Gradual reduction of dose may begin after 12 weeks of initial treatment and may last for up to 12 additional weeks. Strategies recommended by the manufacturer for discontinuing use include the following: Use the inhaler less frequently: Skip doses. Keep a tally of daily usage, and try to meet a steadily reducing target.

NICOTINE INHALER: SCHEMATIC DIAGRAM
Air/nicotine mixture out Sharp point that breaks the seal Aluminum laminate sealing material This schematic diagram depicts the key components of the nicotine inhalation system. The nicotine inhaler consists of a two-piece plastic unit designed to deliver nicotine contained in individual cartridges. Each foil-sealed cartridge contains a porous plug impregnated with 10 mg of nicotine and 1 mg of menthol. Sharp spikes found on the interior of both mouthpiece components pierce the protective foil covering, allowing the release of nicotine vapor following inhalation. Schneider NG, Olmstead RE, Franzon MA, Lunell E. (2001). The nicotine inhaler. Clinical pharmacokinetics and comparison with other nicotine treatments. Clin Pharmacokinet 40:661–684. Sharp point that breaks the seal Mouthpiece Porous plug impregnated with nicotine Nicotine cartridge Air in Reprinted with permission from Schneider et al. (2001). Clinical Pharmacokinetics 40:661–684. Adis International, Inc.

NICOTINE INHALER: DIRECTIONS for USE
Align marks on the mouthpiece ♪ Note to instructor(s): Demonstrate the use of inhaler with a placebo nicotine inhaler. Have each student assemble and use a placebo inhaler unit. Nicotine inhaler: Directions for use Align the marks on the mouthpiece.

NICOTINE INHALER: DIRECTIONS for USE (cont’d)
Pull and separate mouthpiece into two parts Nicotine inhaler: Directions for use (cont’d) Pull and separate the mouthpiece into two parts.

Press nicotine cartridge firmly into bottom of mouthpiece until seal breaks Nicotine inhaler: Directions for use (cont’d) Press the nicotine-containing cartridge firmly into the bottom of the mouthpiece until the seal breaks.

Put top on mouthpiece and align marks to close Press down firmly to break top seal of cartridge Twist top to misalign marks and secure unit Nicotine inhaler: Directions for use (cont’d) Put the top on the mouthpiece and align the marks to close. Press down firmly to break the top seal on the cartridge. Twist the top piece to misalign the marks and secure the unit. The nicotine inhaler is now ready for use.

During inhalation, nicotine is vaporized and absorbed across oropharyngeal mucosa Inhale into back of throat or puff in short breaths Nicotine in cartridges is depleted after about 20 minutes of active puffing Cartridge does not have to be used all at once Open cartridge retains potency for 24 hours Mouthpiece is reusable; clean regularly with mild detergent Nicotine inhaler: Directions for use (cont’d) When inhaled or puffed through the mouthpiece, nicotine turns into a vapor that is absorbed across the oropharyngeal mucosa. Inhale into the back of throat or puff in short breaths. ♪ Note to instructor(s): Patients should be instructed not to inhale into the lungs (like a cigarette) but to puff as if lighting a pipe. Deep inhalation into the lungs increases the delivery of nicotine and increases the incidence of adverse effects. Nicotine in the cartridges is depleted after about 20 minutes of active puffing: The 20-minute supply is not necessarily meant to be used at one time. Patients can use the inhaler for just a few minutes, put it down, and then pick it up later and use it again for a total of 20 minutes of active puffing per cartridge (~ 80 puffs). An open cartridge retains potency for 24 hours. Once opened, each cartridge, whether fully used or not, should be replaced after 24 hours. The mouthpiece is reusable and should be cleaned regularly with a mild detergent and water.

NICOTINE INHALER: ADDITIONAL PATIENT EDUCATION
Patients may experience mild irritation of the mouth or throat, and an unpleasant taste or cough when first using the inhaler Patients will adapt to these effects in a short time Other (less common) side effects include Rhinitis Dyspepsia Hiccups Headache When initiating treatment, patients may experience mild irritation of the mouth or throat (40%), or a cough (32%). Upset stomach (18%) may also occur. In general, patients adapt to these effects after about a week of therapy. The majority of patients rated cough and mouth and throat irritation symptoms as mild, decreasing with continued use. Other (less common) side effects include rhinitis, dyspepsia, hiccups, and headache.

NICOTINE INHALER: ADD’L PATIENT EDUCATION (cont’d)
The inhaler may not be as effective in very cold (<59F) temperatures—delivery of nicotine vapor may be compromised Use the inhaler longer and more often at first to help control cravings (best results are achieved with frequent continuous puffing over 20 minutes) Effectiveness of the nicotine inhaler may be reduced by some foods and beverages Release of nicotine from the porous plug is dependent on the vapor pressure of nicotine, which is dependent on the air temperature passing through the plug. Under colder conditions (<59F), less nicotine is delivered per puff. Conversely, under warmer conditions more nicotine is released per puff. However, nicotine plasma concentrations achieved using the inhaler in hot climates at maximal doses will not exceed levels normally achieved with smoking (Schneider et al., 2001). Best results are achieved with frequent continuous puffing over 20 minutes. The inhaler should be used longer and more often at first to help control cigarette cravings. Less nicotine per puff is released from the inhaler compared to a cigarette. The effectiveness of the nicotine inhaler may be reduced by some foods and beverages, such as coffee, juices, wine, or soft drinks. Therefore, patients should be instructed not to eat or drink for 15 minutes before or while using the inhaler. Acidic beverages may transiently reduce the pH of the saliva below that necessary for optimal buccal absorption of nicotine. Schneider NG, Olmstead RE, Franzon MA, Lunell E. (2001). The nicotine inhaler. Clinical pharmacokinetics and comparison with other nicotine treatments. Clin Pharmacokinet 40:661–684. Do NOT eat or drink for 15 minutes BEFORE or while using the nicotine inhaler.

NICOTINE INHALER: SUMMARY
ADVANTAGES Patients can easily titrate therapy to manage withdrawal symptoms. The inhaler mimics the hand-to-mouth ritual of smoking. DISADVANTAGES The initial throat or mouth irritation can be bothersome. Cartridges should not be stored in very warm conditions or used in very cold conditions. Patients with underlying bronchospastic disease must use the inhaler with caution. Advantages of the nicotine inhaler include the following: Patients can easily titrate therapy to manage withdrawal symptoms. The inhaler mimics the hand-to-mouth ritual of smoking. Disadvantages of the inhaler include the following: Initial throat or mouth irritation (generally in first week) can be bothersome. Cartridges should not be stored in conditions exceeding 86oF or be used below 59oF, because the delivery system may be compromised at temperatures outside this range. Patients with underlying bronchospastic conditions should use the nicotine inhaler with caution. Other forms of NRT may be preferred for patients with severe bronchospastic airway disease (e.g., severe asthma or chronic obstructive pulmonary disease) because the nicotine vapor may be irritating and provoke bronchospasm.

BUPROPION SR Zyban (GlaxoSmithKline); generic
Nonnicotine cessation aid Sustained-release antidepressant Oral formulation FDA approved for smoking cessation: May 1997 (prescription only), generic approved in 2004 Description of Product Bupropion sustained-release (SR) tablets are an oral antidepressant medication used as a nonnicotine aid to smoking cessation. The same chemical agent is marketed as Wellbutrin for use in treating depression. Clinical Efficacy (Hughes et al., 2004) The use of bupropion SR approximately doubles the long-term abstinence rate when compared to placebo. A meta-analysis of 19 studies revealed the following estimated abstinence rates (6 months follow-up): Placebo 10.2% Bupropion SR 20.0% The pooled odds ratio of abstinence for bupropion SR was 2.06 (95% CI, 1.77–2.40) relative to placebo. Hughes JR, Stead LF, Lancaster. (2004). Antidepressants for smoking cessation. Cochrane Database Syst Rev 4:CD

BUPROPION: MECHANISM of ACTION
Atypical antidepressant thought to affect levels of various brain neurotransmitters Dopamine Norepinephrine Clinical effects  craving for cigarettes  symptoms of nicotine withdrawal Bupropion is an atypical antidepressant thought to affect the levels of brain neurotransmitters (e.g., dopamine, norepinephrine). By blocking neural dopamine or norepinephrine uptake in the central nervous system, bupropion decreases the craving for nicotine and symptoms of withdrawal (Fiore et al., 2000). Recall that the dopaminergic system is thought to play a role in self-reinforcing behavior (reward pathways) and dependence, whereas noradrenergic effects are thought to prevent the symptoms of nicotine withdrawal. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service.

BUPROPION: PHARMACOKINETICS
Absorption Bioavailability: 5–20% Metabolism Undergoes extensive hepatic metabolism (CYP2B6) Elimination Urine (87%) and feces (10%) Half-life Bupropion (21 hours); metabolites (20–37 hours) Absorption: Animal data suggest the absolute bioavailability of bupropion ranges from 5 to 20%. Metabolism: Bupropion undergoes extensive hepatic metabolism to three active metabolites. One of the metabolites, hydroxybupropion, is formed by the cytochrome P450 isoenzyme CYP2B6. Elimination: Bupropion and metabolites are eliminated in urine (87%) and feces (10%). Less than 1% of an oral dose of bupropion is excreted unchanged in urine. Half-life: 21 hours (bupropion); 20–37 hours (metabolites). Steady-state plasma concentrations of bupropion and metabolites are reached within 5 and 8 days, respectively. ♪ Note to instructor(s): Because bupropion is extensively metabolized, drug interactions are possible, particularly with agents metabolized by the CYP2D6 isoenzyme including certain antidepressants (e.g., nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide). Although bupropion is not metabolized by cytochrome CYP2D6, drug interactions are possible when bupropion is coadministered with drugs metabolized by this isoenzyme because bupropion and one of its metabolites (hydroxybupropion) are inhibitors of the CYP2D6 isoenzyme in vitro. Drug Interactions Carbamazepine (Tegretol): This drug increases hepatic metabolism of bupropion. Serum concentrations and pharmacologic effects of bupropion may be decreased. Levodopa (Dopar, Sinemet), amantadine (Symmetrel): Limited clinical data suggest a higher incidence of adverse experiences in patients receiving concurrent administration of bupropion with either levodopa or amantadine. Coadministration of bupropion to patients receiving levodopa should be undertaken with caution, using small initial doses and gradual dose increases. Monoamine oxidase (MAO) inhibitors (isocarboxazid [Marplan]), phenelzine [Nardil], tranylcypromine [Parnate]): Animal data suggest the risk of acute bupropion toxicity is increased with coadministration. Do not administer bupropion within 14 days of discontinuing an MAO inhibitor. Drugs that lower the seizure threshold: Concurrent administration of bupropion and agents (e.g., antipsychotics, antidepressants, theophylline, systemic steroids) that lower the seizure threshold should be undertaken only with extreme caution. GlaxoSmithKline Inc. (2006, May). Zyban Package Insert. Research Triangle Park, NC.

BUPROPION: CONTRAINDICATIONS
Patients with a seizure disorder Patients taking Wellbutrin, Wellbutrin SR, Wellbutrin XL MAO inhibitors in preceding 14 days Patients with a current or prior diagnosis of anorexia or bulimia nervosa Patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines) Bupropion is contraindicated in patients with seizure disorders. Although seizures were not reported in the Zyban smoking cessation clinical trials, the incidence of seizures with the sustained-release formulation (Wellbutrin) used in the treatment of depression was 0.1% (i.e., 1/1,000) in patients without a previous history of seizures. Patients taking any form of medication that lowers the seizure threshold should not be given bupropion without close medical monitoring. Bupropion is contraindicated in patients with a current or prior diagnosis of anorexia or bulimia nervosa because of a higher incidence of seizures noted in patients treated for bulimia with the immediate-release formulation of bupropion. Bupropion is the active ingredient in Wellbutrin, Wellbutrin SR, and Wellbutrin XL, which are used in the treatment of depression, and in Zyban, which is used for tobacco cessation. These medications should not be used in combination because the incidence of seizures is dose related. The concurrent administration of bupropion and a monoamine oxidase (MAO) inhibitor is contraindicated. Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAO inhibitor phenelzine. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with bupropion. Bupropion is contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives, including benzodiazepines. ♪ Note to instructor(s): Because the use of bupropion is associated with a dose-dependent risk of seizures, clinicians should not prescribe doses over 300 mg/day for smoking cessation. The seizure rate associated with doses of bupropion SR up to 300 mg/day is approximately 0.1% (1/1,000). This incidence was prospectively determined during an 8-week treatment exposure in approximately 3,100 depressed patients. Data for the immediate-release formulation of bupropion revealed a seizure incidence of approximately 0.4% (4/1,000) in depressed patients treated at doses of 300–450 mg/day. In addition, the estimated seizure incidence increases almost tenfold between 450 and 600 mg/day. Predisposing factors that may increase the risk of seizure with bupropion use include history of head trauma or prior seizure, central nervous system tumor, and concomitant medications that lower the seizure threshold. The risk of seizure may be minimized if the total daily dose does not exceed 300 mg (the maximum recommended dose for smoking cessation) and the recommended daily dose (300 mg) is administered in divided doses (150 mg twice daily). No single dose should exceed 150 mg to avoid high peak concentrations of bupropion or its metabolites. GlaxoSmithKline Inc. (2006, May). Zyban Package Insert. Research Triangle Park, NC.

BUPROPION: WARNINGS and PRECAUTIONS
Bupropion should be used with extreme caution in the following populations: Patients with a history of seizure Patients with a history of cranial trauma Patients taking medications that lower the seizure threshold (antipsychotics, antidepressants, theophylline, systemic steroids) Patients with severe hepatic cirrhosis Bupropion should be used with extreme caution in patients with a history of seizure or cranial trauma, or in patients taking medications that may lower the seizure threshold (e.g., antipsychotics, antidepressants, theophylline, systemic steroids). Bupropion also should be used with extreme caution in patients with severe hepatic cirrhosis. In these patients a reduced frequency of dosing is required, because peak bupropion levels are substantially increased and accumulation is likely to occur to a greater extent than usual in such patients. The dose should not exceed 150 mg every other day in these patients. GlaxoSmithKline Inc. (2006, May). Zyban Package Insert. Research Triangle Park, NC.

BUPROPION: USE in PREGNANCY
Category C drug Use only if clearly indicated Attempt nondrug treatment first The FDA has recently re-classified bupropion as a pregnancy category C drug, meaning either (a) animal studies have demonstrated that the drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or (b) no studies are available in either animals or women. This change in labeling was based on an FDA reanalysis of pre-clinical animal data demonstrating an increase in the incidence of fetal malformations and skeletal variations among rabbits receiving dosages approximately two-fold higher than the maximum recommended human dose (on a mg/m2 basis) of bupropion. The manufacturer recommends that bupropion be used during pregnancy only if clearly needed (GlaxoSmithKline, 2006a). ♪ Note to instructor(s): The manufacturer of Zyban (GlaxoSmithKline) has maintained a bupropion pregnancy registry since September 1997, and interim reports are published every 6 months. As of February 28, 2006 a total of 1,347 pregnancies have been registered, and data are available for 783 pregnancy outcomes. * Risk for birth defects calculated by dividing the number of live births, fetal deaths, and induced abortions with birth defects by the combined number of live births without birth defects and all outcomes with reported birth defects. Fetal deaths and induced abortions without reported birth defects as well as spontaneous pregnancy losses were excluded from this calculation (GlaxoSmithKline, 2006b). The registry data do not suggest an increased prevalence of birth defects among fetuses exposed to bupropion when compared to the baseline frequency of birth defects observed among the general population (approximately 3%) (GlaxoSmithKline, 2006b). Although the limited data available suggest that bupropion use is safe during pregnancy, clinicians should be aware that the current sample size is insufficient for reaching reliable and definitive conclusions regarding the risk of bupropion to a developing fetus (GlaxoSmithKline, 2006b). For this reason, bupropion therapy should be reserved for women who are unable to quit smoking using behavioral interventions alone. GlaxoSmithKline Inc. (2006a, May). Zyban Package Insert. Research Triangle Park, NC. GlaxoSmithKline. (2006b, June). The bupropion pregnancy registry. Interim report 1 September 1997 through 28 February Wilmington, NC. For Information on obtaining the report, see Earliest bupropion exposure (n) Number of birth defects reported (%)* 1st trimester (n=621) 20 (3.9%) 2nd trimester (n=113) 2 (1.8%) 3rd trimester (n=49) 0 (0%)

Patients should begin therapy 1 to 2 weeks PRIOR
BUPROPION SR: DOSING Patients should begin therapy 1 to 2 weeks PRIOR to their quit date to ensure that therapeutic plasma levels of the drug are achieved. Initial treatment 150 mg po q AM x 3 days Then… 150 mg po bid Duration, 7–12 weeks Treatment with bupropion SR should be initiated while the patient is still smoking, because approximately 1 week of treatment is required to achieve steady-state blood levels. Patients should set a target quit date that falls within the first 2 weeks of treatment, generally in the second week (GlaxoSmithKline, 2006). The starting dose of bupropion SR is one 150-mg tablet each morning for the first 3 days. If the initial dose is tolerated adequately, the dosage should be increased on day 4 to the recommended, maximum dosage of 300 mg/day, given as two 150-mg doses taken at least 8 hours apart. Doses above 300 mg/day should not be used. Duration of therapy is recommended to be 7–12 weeks; however, some patients may benefit from extended treatment. Systematic evaluation of bupropion SR 300mg per day for maintenance therapy demonstrated that treatment for up to 6 months was efficacious (GlaxoSmithKline, 2006). Whether to continue treatment with bupropion for periods longer than 12 weeks (3 months) for smoking cessation must be determined for individual patients. In selected patients, maintenance treatment up to 12 months may be appropriate (Hays et al., 2003). ♪ Note to instructor(s): For patients experiencing side effects with the 300 mg/day regimen, Swan et al. (2003) suggest that 150 mg/day is better tolerated and exhibits comparable long-term efficacy. Similarly, Hurt and colleagues (1997) found no significant difference in long-term (>6 months) abstinence rates between subjects randomized to 150 mg/day or 300 mg/day. GlaxoSmithKline Inc. (2006, May). Zyban Package Insert. Research Triangle Park, NC. Hays JT, Hurt RD, Rigotti NA, et al. (2001). Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. a randomized, controlled trial. Ann Intern Med 135:423–433. Hurt RD, Sachs DP, Glover ED, et al. (1997). A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 337:1195–1202. Swan GE, McAfee T, Curry SJ, et al. (2003). Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial. Arch Intern Med 163:2337–2344.

BUPROPION: ADVERSE EFFECTS
Common side effects include the following: Insomnia (avoid bedtime dosing) Dry mouth Less common but reported effects: Tremor Skin rash Common side effects include insomnia (31–45%) and dry mouth (9–11%). These side effects usually lessen with continued use. Patients should be advised to avoid taking bupropion at bedtime. Side effects that are less common but are associated with discontinuation of treatment include nervous system disturbances (3.4%; primarily tremors) and skin disorders (2.4%; primarily rashes) (GlaxoSmithKline, 2006). GlaxoSmithKline Inc. (2006, May). Zyban Package Insert. Research Triangle Park, NC.

BUPROPION: ADDITIONAL PATIENT EDUCATION
Dose tapering not necessary when discontinuing treatment If no significant progress toward abstinence by seventh week, therapy is unlikely to be effective Discontinue treatment Reevaluate and restart at later date Dose tapering of bupropion SR is not required when discontinuing treatment. If a patient has not made significant progress toward abstinence by the seventh week of therapy with bupropion SR, he or she is unlikely to quit during that attempt and treatment should be discontinued. Patients who are unsuccessful should be evaluated to determine why they relapsed, and a new quit attempt should be encouraged when conditions are more favorable.

BUPROPION SR: SUMMARY ADVANTAGES DISADVANTAGES
Bupropion is an oral formulation with twice-a-day dosing. Bupropion might be beneficial for patients with depression. DISADVANTAGES The seizure risk is increased. Several contraindications and precautions preclude use. Advantages of bupropion SR include the following: Bupropion SR is an oral formulation (twice-a-day dosing) that is easy to use. Bupropion SR might be beneficial for use in patients with coexisting depression. There is no risk of nicotine toxicity if the patient continues to smoke. Disadvantages of bupropion SR include the following: The seizure risk is increased. Several contraindications and precautions preclude use.

VARENICLINE Chantix (Pfizer)
Nonnicotine cessation aid Partial nicotinic receptor agonist Oral formulation FDA approved for smoking cessation: May 11, 2006 (prescription only) Description of Product (Pfizer, 2006) Varenicline is a partial agonist selective for the 42 nicotinic acetylcholine receptor indicated for use as an aid to smoking cessation treatment. Clinical Efficacy Data from three published trials (summarized below) suggest the use of varenicline significantly increases long-term abstinence rates relative to placebo (Gonzales et al., 2006; Jorenby et al., 2006; Tonstad et al., 2006) and bupropion SR (Jorenby et al., 2006). The pooled odds ratio for varenicline versus placebo (continuous abstinence at 12 months) is 2.8 (95% CI, 2.0–3.9). a Subjects were randomly assigned to receive active drug or placebo for 12 weeks. b Subjects successfully quitting after 12 weeks of open-label varenicline treatment were randomly assigned to receive an additional 12 weeks of varenicline or placebo. Pfizer, Inc. (2006, May). Chantix Package Insert. New York, NY. Gonzales D, Rennard SI, Nides M, et al. (2006). Varenicline, an 4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 296:47-55. Jorenby DE, Hays JT, Rigotti NA, et al. (2006). Efficacy of varenicline, an 4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 296:56-63. Tonstad S, Tonnesen P, Hajek P, et al. (2006). Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA 296:64-67. Continuous Smoking Abstinence Rates at Week 52 Follow-up (%) Varenicline 1mg bid Bupropion SR 150mg bid Placebo Gonzales et al. (n=1025)a 21.9 16.1 8.4 Jorenby et al. (n=1027)a 23.0 14.6 10.3 Tonstad et al. (n=1210)b 43.6 - 36.9

VARENICLINE: MECHANISM of ACTION
Binds with high affinity and selectivity at 42 neuronal nicotinic acetylcholine receptors Stimulates low-level agonist activity Competitively inhibits binding of nicotine Clinical effects  symptoms of nicotine withdrawal Blocks dopaminergic stimulation responsible for reinforcement & reward associated with smoking Varenicline binds with high affinity and selectivity at 42 neuronal nicotinic acetylcholine receptors. The efficacy of varenicline in smoking cessation is believed to be the result of low-level agonist activity at the receptor site combined with competitive inhibition of nicotine binding. The partial agonist activity induces modest receptor stimulation that attenuates the symptoms of nicotine withdrawal. In addition, by blocking the ability of nicotine to activate 42 nicotinic acetylcholine receptors, varenicline inhibits the surges of dopamine release that are believed to be responsible for the reinforcement and reward associated with smoking (Foulds, 2006; Pfizer, 2006). Foulds J. (2006). The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline. Int J Clin Pract 60:571–576. Pfizer, Inc. (2006, May). Chantix Package Insert. New York, NY.

VARENICLINE: PHARMACOKINETICS
Absorption Virtually complete after oral administration; not affected by food Metabolism Undergoes minimal metabolism Elimination Primarily renal through glomerular filtration and active tubular secretion; 92% excreted unchanged in urine Half-life 24 hours Absorption: absorption is virtually complete after oral administration, and oral bioavailability is unaffected by food or time-of-day dosing. Metabolism: Varenicline undergoes minimal metabolism, with 92% excreted unchanged in the urine. Elimination: Renal elimination of varenicline is primarily through glomerular filtration along with active tubular secretion possibly via the organic cation transporter, OCT2. Half-life: ~24 hours; following administration of multiple oral doses of varenicline, steady-state conditions are reached within 4 days. Pfizer, Inc. (2006, May). Chantix Package Insert. New York, NY.

VARENICLINE : USE in PREGNANCY and LACTATION
Category C drug Use only if potential benefit justifies potential risk Attempt nondrug treatment first Unknown if drug excreted in human breast milk The FDA has classified varenicline as a pregnancy category C drug, meaning either (a) animal studies have demonstrated that the drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or (b) no studies are available in either animals or women. The manufacturer recommends that varenicline be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (Pfizer, 2006). It is not known whether varenicline is excreted in human breast milk. The manufacturer states that because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pfizer, Inc. (2006, May). Chantix Package Insert. New York, NY.

Patients should begin therapy 1 week PRIOR to their
VARENICLINE: DOSING Patients should begin therapy 1 week PRIOR to their quit date. The dose is gradually increased to minimize treatment-related nausea and insomnia. Treatment Day Dose Day 1 to day 3 0.5 mg qd Day 4 to day 7 0.5 mg bid Day 8 to end of treatment* 1 mg bid Treatment with varenicline should be initiated one week BEFORE the patient stops smoking. This dosing regimen allows for gradual titration of the dose to minimize treatment-related nausea and insomnia. The recommended dose of varenicline is 1mg bid (taken as one 1mg tablet in the morning and one 1mg tablet in the evening) following a 1-week titration as follows: Treatment Day Dose Days 1– mg qd Days 4– mg bid Weeks 2– mg bid The manufacturer recommends that the dosage may be lowered temporarily or permanently for patients experiencing intolerable treatment-associated adverse effects. Patients should be treated with varenicline for 12 weeks. For patients who have successfully quit smoking at the end of 12 weeks, an additional course of 12 weeks may be appropriate to increase the likelihood of long-term abstinence. ♪ Note to instructor(s): Per the manufacturer’s prescribing information, the recommended dosage of varenicline for children, elderly patients, and individuals with impaired renal or hepatic function is as follows: Use in children Safety and effectiveness in pediatric patients have not been established; therefore, varenicline is not recommended for use in patients under 18 years of age. Dosing in elderly patients and patients with impaired hepatic function No dosage adjustment is necessary for patients with hepatic impairment. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Patients with impaired renal function No dosage adjustment is necessary for patients with mild to moderate renal impairment. For patients with severe renal impairment (estimated creatinine clearance <30 mL/min), the recommended starting dose is 0.5 mg once daily. Patients may then titrate as needed to a maximum dose of 0.5 mg twice a day. For patients with end-stage renal disease undergoing hemodialysis, a maximum dose of 0.5 mg once daily may be administered if tolerated well. Pfizer, Inc. (2006, May). Chantix Package Insert. New York, NY. Initial dose titration * Up to 12 weeks

VARENICLINE: ADVERSE EFFECTS
Common side effects (≥5% and twice the rate observed in placebo-treated patients) include: Nausea Sleep disturbances (insomnia, abnormal dreams) Constipation Flatulence Vomiting Common side effects (≥5% and twice the rate observed in placebo-treated patients) include: Nausea (30%) Sleep disturbance (insomnia 18%; abnormal dreams 13%) Constipation (8%) Flatulence (6%) Vomiting (5%) ♪ Note to instructor(s): Per the manufacturer’s prescribing information, nausea was the most common adverse event associated with varenicline treatment. Nausea was generally described as mild or moderate and often transient; however, for some subjects, it was persistent over several months. The incidence of nausea was dose-dependent. Initial dose titration was beneficial in reducing the occurrence of nausea. Approximately 3% of subjects receiving varenicline 1 mg bid discontinued treatment prematurely because of nausea. For patients with intolerable nausea, dose reduction should be considered. Pfizer, Inc. (2006, May). Chantix Package Insert. New York, NY.

VARENICLINE: ADDITIONAL PATIENT EDUCATION
Doses should be taken after eating, with a full glass of water Nausea and insomnia are side effects that are usually temporary. If symptoms persist, notify your health care provider Dose tapering not necessary when discontinuing treatment Doses should be taken after eating, with a full glass of water. Nausea and insomnia are side effects that are usually temporary. However, if these symptoms persist, notify your provider so dosage reduction can be considered. Dose tapering is not necessary when discontinuing treatment. Pfizer, Inc. (2006, May). Chantix Package Insert. New York, NY.

VARENICLINE: SUMMARY ADVANTAGES DISADVANTAGES
Varenicline is an oral formulation with twice-a-day dosing. Varenicline offers a new mechanism of action for persons who previously failed using other medications. DISADVANTAGES May induce nausea in up to one third of patients. Post-marketing surveillance data not yet available. Advantages of varenicline include the following: Varenicline is an oral formulation (twice-a-day dosing) that is easy to use. Varenicline offers a new mechanism of action for persons who previously failed using other medications. Disadvantages of varenicline include the following: The drug may induce nausea in up to one third of patients. Post-marketing surveillance data not yet available.

PHARMACOLOGIC METHODS: SECOND-LINE THERAPIES
Clonidine (Catapres transdermal or oral) Nortriptyline (Pamelor oral) Second-line medications are efficacious for treating tobacco dependence but should not be used initially because (a) they are not FDA approved for tobacco cessation and (b) they have a greater incidence of adverse effects. For these reasons, clonidine and nortriptyline should be reserved for patients unable to use first-line medications (Fiore et al., 2000). Clonidine (Catapres) is a centrally acting α2-adrenergic agonist that reduces sympathetic outflow from the central nervous system. It is approved for use as an antihypertensive agent but is also effective in reducing the autonomic symptoms of both opioid and alcohol withdrawal. Studies of clonidine for smoking cessation have been inconsistent, but a recent meta-analysis of six trials concluded that clonidine was an effective agent for tobacco cessation. The pooled odds ratio for success with clonidine was 1.89 (95% CI, 1.30–2.74) relative to placebo (Gourlay et al., 2004). Side effects: The most commonly reported adverse effects include dry mouth, drowsiness, dizziness, sedation, and constipation. Given its antihypertensive properties, clonidine can be expected to lower blood pressure in most patients. Monitoring of blood pressure may be necessary. Precautions and contraindications: Patients should be tapered off of clonidine (over 2–4 days), because abrupt termination might lead to rebound hypertension. It must be used with caution in patients who have reduced ventricular function, slow heart rate, or AV node conduction problems. FDA pregnancy class C drug. Dosage regimen: Dosages for tobacco cessation have ranged from 0.15 to 0.75 mg/day orally and from 0.1 to 0.3 mg/day per day transdermally. The Clinical Practice Guideline recommends a starting dose of 0.1 mg orally twice daily or 0.1 mg/day transdermally, increasing by 0.10 mg/day per week as tolerated. The duration of therapy has varied across clinical trials, from 3 to 10 weeks. Available only by prescription. Nortriptyline (Aventyl, Pamelor) is a tricyclic antidepressant with demonstrated efficacy for smoking cessation in four long-term (6- to 12-month) studies. The pooled odds ratio of quitting was 2.79 (95% CI, 1.70–4.59) relative to placebo (Hughes et al., 2004). Side effects: The primary side effects are sedation, dry mouth, blurred vision, urinary retention, lightheadedness, and tremor. Precautions and contraindications: It must be used with caution in patients with underlying cardiovascular conditions due to the risk of arrhythmias and postural hypotension. FDA pregnancy class D drug. Dosage regimen: The regimens studied for smoking cessation have typically started at a dose of 25 mg at bedtime, increasing gradually to a target dose of 75–100 mg/day for 6–10 weeks; most trials gradually tapered the dosage over an additional 1–2 weeks. Because the half-life of the drug is prolonged (up to 54 hours), therapy is initiated prior to the quit date to allow nortriptyline to reach therapeutic steady-state concentrations. In clinical trials, nortriptyline has been initiated 10–28 days before the quit date. Available only by prescription. Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Gourlay SG, Stead LF, Benowitz NL. (2004). Clonidine for smoking cessation. Cochrane Database Syst Rev 3:CD Hughes JR, Stead LF, Lancaster. (2004). Antidepressants for smoking cessation. Cochrane Database Syst Rev 4:CD

HERBAL DRUGS for SMOKING CESSATION
Lobeline Derived from leaves of Indian tobacco plant (Lobelia inflata) Partial nicotinic agonist No scientifically rigorous trials with long-term follow-up No evidence to support use for smoking cessation Although a variety of herbal and homeopathic products are available to aid cessation, data are lacking to support their safety and efficacy. Many herbal preparations for smoking cessation contain lobeline (Lobelia inflata), an herbal alkaloid with partial nicotinic agonist properties. Nonprescription, lobeline-containing products were banned by the FDA in 1993 due to a lack of efficacy. Although lobeline remains available as a dietary supplement, a meta-analysis of trials published in the preceding 60 years found no evidence to support the role of lobeline as an aid for smoking cessation (Stead & Hughes, 1997). Studies of lobeline were largely uncontrolled and short-term (<6 months), and they used outcome measures such as the percentage reduction in the number of cigarettes smoked, rather than complete abstinence (Stead & Hughes, 1997). ♪ Note to instructor(s): Herbal smoking cessation medications containing lobeline include CigArrest, Smoke Away, and NicoRx. Stead LF, Hughes JR. (1997). Lobeline for smoking cessation. Cochrane Database Syst Rev 3:CD Illustration courtesy of Missouri Botanical Garden ©

LONG-TERM (6 month) QUIT RATES for AVAILABLE CESSATION MEDICATIONS
23.9 22.4 19.5 20.0 17.1 16.4 Few head-to-head trials have compared the various tobacco cessation therapies. In a randomized controlled trial comparing the four NRT formulations available at the time, the products performed similarly, but patient compliance was higher with the patch, followed by the gum, which was higher than the inhaler and nasal spray (Hajek et al., 1999). This bar chart summarizes the long-term (6-month) quit rates observed with the different NRT products, bupropion SR and varenicline (Gonzales et al., 2006; Hughes et al., 2004; Jorenby et al., 2006; Silagy et al., 2004). These data derive from 124 different placebo-controlled trials; therefore, it is inappropriate to compare the active medications with respect to clinical efficacy. What this chart does illustrate, however, is that the quit rates from each of the methods is approximately twice that of its corresponding placebo control treatment arm. Each of the pharmacotherapy options depicted in the chart is considered effective. When patients ask for assistance with their quit attempt, any product can be recommended, if not contraindicated. However, when assisting patients in choosing a product, clinicians should consider additional factors. The number of cigarettes smoked per day (or time to first cigarette, for the nicotine lozenge), level of dependence, advantages and disadvantages of each product, methods used for prior quit attempts and reasons for relapse, and the patient’s own product preference need to be considered. Behavioral counseling should be used in conjunction with all pharmacologic therapies. Gonzales D, Rennard SI, Nides M, et al. (2006). Varenicline, an 4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 296:47-55. Hajek P, West R, Foulds J, Nilsson F, Burrows S, Meadow A. (1999). Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med 159:2033–2038. Hughes JR, Stead LF, Lancaster. (2004). Antidepressants for smoking cessation. Cochrane Database Syst Rev 4:CD Jorenby DE, Hays JT, Rigotti NA, et al. (2006). Efficacy of varenicline, an 4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 296:56-63. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD 14.6 Percent quit 11.5 11.8 10.2 8.6 8.8 9.1 9.3 Data adapted from Silagy et al. (2004). Cochrane Database Syst Rev; Hughes et al., (2004). Cochrane Database Syst Rev.; Gonzales et al., (2006). JAMA and Jorenby et al., (2006). JAMA

COMBINATION PHARMACOTHERAPY
Reserve for patients unable to quit using monotherapy. Combination NRT Long-acting formulation (patch) Produces relatively constant levels of nicotine PLUS Short-acting formulation (gum, lozenge, inhaler, nasal spray) Allows for acute dose titration as needed for withdrawal symptoms Bupropion SR + NRT The safety and efficacy of combination of varenicline with NRT or bupropion has not been established. Combination NRT Combination NRT involves the use of a long-acting formulation (patch) in combination with a short-acting formulation (gum, lozenge, inhaler, or nasal spray). The long-acting formulation, which delivers relatively constant levels of drug, is used to prevent the onset of severe withdrawal symptoms, and the short-acting formulation, which delivers nicotine at a faster rate, is used as needed to control withdrawal symptoms that may occur during potential relapse situations (e.g., after meals, when under stress, or when around other smokers). A recent meta-analysis of seven trials found a statistically significant benefit among smokers randomized to combination NRT (Silagy et al., 2004). The pooled odds ratio for abstinence with combination NRT was 1.42 (95% CI, 1.14–1.76) compared to single-agent NRT. Despite these encouraging results, because of the increased risk of nicotine toxicity and lack of long-term safety data, combination NRT should be reserved for patients unable to quit using single-agent NRT (Fiore et al., 2000). Clinicians should be aware that NRT products are not FDA approved for dual use and that the optimal combinations, dosages, and duration of therapy for this more aggressive approach are unknown. NRT and Bupropion SR Combination Therapy Combination therapy with bupropion SR and NRT has been evaluated in two controlled trials. Both trials compared the combination of bupropion SR and the nicotine patch (21 mg tapered over 8 weeks). In one trial, the 1‑year abstinence rates were higher with combination therapy (35.5%) than with bupropion SR alone (30.3%), but the difference was not statistically significant (Jorenby, 1999). In contrast, Simon et al. (2004) observed higher (but not statistically significant) 1-year abstinence rates among smokers randomized to nicotine patch monotherapy (24%) versus bupropion SR in combination with the nicotine patch (19%). Recently, encouraging results were observed in an open label trial evaluating combination therapy with the nicotine inhaler, nicotine patch, nicotine nasal spray, and bupropion SR. Patients were prescribed escalating dosages of NRT (in combination) based on baseline cigarette consumption; individuals with severe tobacco cessation anxiety received bupropion SR in addition to the NRT. At 12 months, 37% of the subjects had remained abstinent and there were no serious adverse effects observed (Bars et al., 2006). Although the combination of NRT and bupropion appears to be safe, further controlled studies are needed to identify the optimal combinations, dosages, and duration for this treatment approach. Combination with Varenicline The safety and effectiveness of varenicline in combination with bupropion SR or NRT has not be established. In a small study (n=39 subjects) evaluating varenicline (1 mg bid) in combination with the nicotine patch (21 mg/day) for up to 12 days the incidence of nausea, headache, vomiting, dizziness, dyspepsia and fatigue were greater for the combination when compared to the patch alone. Patients receiving the combination were 6-times as likely to prematurely discontinue treatment due to adverse events compared to those taking NRT monotherapy (Pfizer, 2006). Bars MP, Banauch GI, Appel D, Andreachi M, Mouren P et al. (2006). "Tobacco Free With FDNY": the New York City Fire Department World Trade Center Tobacco Cessation Study. Chest 129: Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Jorenby DE, Leischow SJ, Nides MA, et al. (1999). A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 340:685–691. Pfizer, Inc. (2006, May). Chantix Package Insert. New York, NY. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD Simon JA, Duncan D, Carmody TP, Hudes ES. (2004). Bupropion for smoking cessation: a randomized trial. Arch Intern Med 164:1797–1803.

COMPLIANCE IS KEY to QUITTING
Promote compliance with prescribed regimens. Use according to dosing schedule, NOT as needed. Consider telling the patient: “When you use a cessation product it is important to read all the directions thoroughly before using the product. The products work best in alleviating withdrawal symptoms when used correctly, and according to the recommended dosing schedule.” Comprehensive counseling not only provides patients with information and social support for their quit attempts, but it also could improve the poor compliance rates commonly observed with treatment regimens for cessation (Hajek et al., 1999; Pierce & Gilpin, 2002; Schneider et al., 2003). When counseling quitters for pharmacotherapy, particularly NRT, it is important to emphasize the need to use the products correctly and to adhere to the recommended dosing schedule. Hajek P, West R, Foulds J, Nilsson F, Burrows S, Meadow A. (1999). Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med 159:2033–2038. Pierce JP, Gilpin EA. (2002). Impact of over-the-counter sales on effectiveness of pharmaceutical aids for smoking cessation. JAMA 288:1260–1264. Schneider MP, van Melle G, Uldry C, Huynh-Ba M, Fallab Stubi CL, Iorillo D, et al. (2003). Electronic monitoring of long-term use of the nicotine nasal spray and predictors of success in a smoking cessation program. Nicotine Tob Res 5:719–727.

COMPARATIVE DAILY COSTS of PHARMACOTHERAPY
$6.07 $5.81 $5.73 This slide presents the approximate daily costs of treatment for the various pharmacotherapies for cessation. These are estimates* based on the recommended initial dosing for each agent. Costs can vary considerably depending on the patient’s level of smoking, degree of nicotine dependence, product selection (trade versus generic), and need for additional doses of short-acting NRT (gum, lozenge, nasal spray, or oral inhaler). As a comparison, the cost for one pack of cigarettes (national average, approximately $4.26) is shown (Campaign for Tobacco-Free Kids, 2006). In general, the daily cost of pharmacotherapy approximates the cost of one pack of cigarettes. For more exact estimates, refer to the Pharmacologic Product Guide. *Cost calculated using the most expensive average wholesale price for each agent (Drug Topics Redbook, 2006). Campaign for Tobacco-Free Kids. (2006). “State Cigarette Excise Tax Rates & Rankings.” Retrieved December 31, 2006, from Drug Topics Redbook. (2006, December). Montvale, NJ: Medical Economics Company, Inc. $5.26 $4.26 $4.22 $3.91 $3.67 Cost per day, in U.S. dollars

WORKSHOP: CASE SCENARIOS
This section provides instruction on conducting the role-playing exercises.

LEARNING FORMAT Case scenarios
Range of 1–15 minutes for each interaction Two roles Clinician Patient We have provided a series of case scenarios. On average, these should take about 3 minutes for each interaction, although the preparation and action stages will take longer. For each case scenario, two roles are to be played: the clinician and the patient. ♪ Note to instructor(s): Have the students refer to the Tobacco Cessation Counseling Guidesheet and the Pharmacologic Product Guide during this part of the training. These succinct references are very helpful during the role-playing exercises.

LEARNING FORMAT (cont’d)
Break into groups of two Alternate roles as the clinician and the patient Class discussion following each case The class is to break up into groups of two. In each group, one student will play the clinician and the other will play the patient. These roles are to be alternated, within groups. After each case scenario, the class should debrief as a group, discussing what worked and what didn’t.

The CLINICIAN Brief description of the patient and the setting
Tailor your messages based on each patient’s needs and readiness Step 1: ASK about tobacco use Step 2: ADVISE patient to quit Clear, strong, personalized, sensitive Step 3: ASSESS readiness to make a quit attempt The clinician handout includes a brief description of the patient and the setting. If you are playing the clinician’s role, remember to tailor your messages based on the patient’s needs and readiness to quit. When appropriate, ASK about tobacco use, ADVISE the patient to quit, and ASSESS his or her readiness to quit.

The CLINICIAN (cont’d)
Step 4: ASSIST with the quit attempt Assess tobacco use history Assess key issues for the upcoming or current quit attempt Help patient to choose methods for quitting and facilitate the quitting process Step 5: ARRANGE follow-up care Schedule a time to either meet or call patient ASSIST the patient with quitting, if appropriate. This involves assessing the patient’s tobacco use history and key issues for the upcoming or current quit attempt, helping the patient to select method(s) for quitting, and facilitating the quitting process. Finally, ARRANGE appropriate follow-up. These steps are described in the Tobacco Cessation Counseling Guidesheet.

The CLINICIAN (cont’d)
A few helpful hints… Use ACTIVE listening and open-ended questions Show EMPATHY EXPLORE patients’ history, beliefs, motivations, and perceived barriers prior to making recommendations; consider cost issues RESIST temptation to move patients too quickly Refer to TOBACCO CESSATION COUNSELING GUIDESHEET The following are a few helpful hints for the clinician: Be a good listener. When possible, ask open-ended questions (i.e., avoid questions that have yes-no answers). This will help you to learn more about your patients. Demonstrate empathy in your counseling interactions. Respect your patients’ perceptions; otherwise, they will not feel comfortable entrusting you as their tobacco cessation advocate. Before making any recommendations, fully explore your patients’ history, beliefs, motivations, and perceived barriers to quitting. Do not assume that patients can afford the cost of medications for cessation. Be careful in how you word your queries; you do not want to put patients on the defensive. Finally, resist the temptation to move patients too quickly. Change is a process. Moving forward one stage at a time is acceptable and should be viewed as a success. If a patient who comes in wants to quit immediately, help him or her to do so. But most patients that you talk to will not be ready to quit.

The PATIENT Brief description of the patient and the setting
General guidelines for responses to clinician’s queries The patient information sheet for each case provides general guidelines for responses to the clinician’s queries. These are guidelines only; they are not intended to provide every answer to every question the clinician will ask. Answers are provided for a few questions so that the entire class can be working simultaneously (although in different groups) on the same scenario—this will help with the debriefing session after each case.

SUMMARY: CASE SCENARIOS
Use this class time to apply your new knowledge and practice your new counseling skills. Many of the counseling skills learned in the Rx for Change program can be applied to behaviors other than tobacco use Don’t wait too long to apply your new skills in the “real world” Advise students to use this dedicated class time to apply their new knowledge and practice their new counseling skills. The approaches learned in this program can be applied to health behaviors other than tobacco use. Encourage students to apply their new skills, outside of the classroom, in the near future.

Rx for CHANGE Clinician-Assisted Tobacco Cessation

Similar presentations

Presentation on theme: "Rx for CHANGE Clinician-Assisted Tobacco Cessation"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Rx for CHANGE Clinician-Assisted Tobacco Cessation

Similar presentations

Presentation on theme: "Rx for CHANGE Clinician-Assisted Tobacco Cessation"— Presentation transcript:

Similar presentations

About project

Feedback